Exploring the Impact of Intermolecular Interactions on the Glassy Phase Formation of Twist-Bend Liquid Crystal Dimers: Insights from Dielectric Studies.

The formation of the nematic to twist-bend nematic (NTB) phase has emerged as a fascinating phenomenon in the field of supramolecular chemistry, based on complex intermolecular interactions. Through a careful analysis of molecular structures and dynamics, we elucidate how these intermolecular interactions drive the complex twist-bend modulation observed in the NTB. The study employs broadband dielectric spectroscopy spanning frequencies from 10 to 2 × 109 Hz to investigate the molecular orientational dynamics within the glass-forming thioether-linked cyanobiphenyl liquid crystal dimers, namely, CBSC7SCB and CBSC7OCB. The experimental findings align with theoretical expectations, revealing the presence of two distinct relaxation processes contributing to the dielectric permittivity of these dimers. The low-frequency relaxation mode is attributed to an "end-over-end rotation" of the dipolar groups parallel to the director. The high-frequency relaxation mode is associated with precessional motions of the dipolar groups about the director. Various models are employed to describe the temperature-dependent behavior of the relaxation times for both modes. Particularly, the critical-like description via the dynamic scaling model seems to give not only quite good numerical fittings, but also provides a consistent physical picture of the orientational dynamics in accordance with findings from infrared (IR) spectroscopy. Here, as the longitudinal correlations of dipoles intensify, the m1 mode experiences a sudden upsurge in enthalpy, while the m2 mode undergoes continuous changes, displaying critical mode coupling behavior. Interestingly, both types of molecular motion exhibit a strong cooperative interplay within the lower temperature range of the NTB phase, evolving in tandem as the material's temperature approaches the glass transition point. Consequently, both molecular motions converge to determine the glassy dynamics, characterized by a shared glass transition temperature, Tg.

Novel Anti Double-Stranded Nucleic Acids Full-Length Recombinant Camelid Heavy-Chain Antibody for the Detection of miRNA.

The discovery that certain diseases have specific miRNA signatures which correspond to disease progression opens a new biomarker category. The detection of these small non-coding RNAs is performed routinely using body fluids or tissues with real-time PCR, next-generation sequencing, or amplification-based miRNA assays. Antibody-based detection systems allow an easy onset handling compared to PCR or sequencing and can be considered as alternative methods to support miRNA diagnostic in the future. In this study, we describe the generation of a camelid heavy-chain-only antibody specifically recognizing miRNAs to establish an antibody-based detection method. The generation of nucleic acid-specific binders is a challenge. We selected camelid binders via phage display, expressed them as VHH as well as full-length antibodies, and characterized the binding to several miRNAs from a signature specific for dilated cardiomyopathy. The described workflow can be used to create miRNA-specific binders and establish antibody-based detection methods to provide an additional way to analyze disease-specific miRNA signatures.

Thymic activity in immune recovery after allogeneic hematopoietic stem cell transplantation in children.

Thymic output was studied prospectively in 52 children who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Thymic activity was assessed by quantification of recent thymic emigrants (RTE) discriminated from the rest of naive T cells by immunophenotype CD3+/CD4+/CD31+/CD45RA+. Thymic output was analyzed in correlation with the kinetics of immune recovery and in relation to other potential risk factors that may influence thymopoiesis: underlying disease, type of HSCT, source of stem cells, age of recipient and donor, type of conditioning, implemented graft versus host disease (GvHD) prophylaxis, viral reactivations (herpes viruses cytomegalovirus - CMV, Epstein-Barr virus - EBV, adenovirus - ADV, BK virus - BKV), occurrence and grade of both acute and chronic graft versus host disease (aGvHD, cGvHD) and number of transplanted CD34 cells/kg. The absolute count of RTE in peripheral blood was evaluated at 6 time points: before the conditioning and on days +15, +30, +60 , +90 and +180 after HSCT. Occurrence of grade II-IV aGvHD was the most important factor associated with low RTE counts after HSCT. History of malignant disease, and transplantation from matched unrelated donor were risk factors for lower thymic output. We found a weak inverse correlation between the age of the recipient and thymic output on post-HSCT day +180. Source of stem cells, type of conditioning, viral reactivations, occurrence of chronic GvHD, age of the donor and the number of transplanted CD34 cells/kg did not affect thymopoiesis in our study group. These preliminary findings and identification of risk factors for deterioration of thymic activity may in the future help in selecting candidates for thymus rejuvenation strategies.

Analysis of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and mean platelet volume to platelet count ratio in children with acute stage of immunoglobulin A vasculitis and assessment of their suitability for predicting the course of the disease.

Immunoglobulin A vasculitis (IgAV) is the most common systemic vasculitis in developmental age. The disease is most often characterized by a self-limiting course and good prognosis, but sometimes serious complications, like gastrointestinal bleeding or glomerulonephritis, may develop. The neutrophil to lymphocyte (NLR) and the platelet to lymphocyte (PLR) ratios are indicators related to clinical outcome in various inflammatory diseases. The mean platelet volume to platelet count ratio (MPR) has not been evaluated in patients with IgAV. The aim of this study was to analyze the values of the NLR, PLR and MPR in patients with an acute stage of IgAV compared to healthy children and to assess their suitability for predicting the severity of the disease. All children with IgAV hospitalized in our institution between 2012 and 2017 were reviewed retrospectively. The selected laboratory data were recorded before starting the treatment; these results allowed for NLR, PLR, and MPR calculation. The study involved 71 IgAV children. 57.7% of patients revealed signs of systemic involvement (including GT bleeding and/or glomerulonephritis) and 42.3% were nonsystemic (presenting skin and joint symptoms). 83% of patients were classified as mild and 17% as severe course of the disease. The NLR and the PLR were significantly higher in all IgAV children and in the systemic involvement group in comparison with non-systemic. The MPR was significantly lower in all IgAV group with the exception of children without systemic involvement. The NLR is a more valuable indicator than the PLR to identify patients at higher risk of systemic involvement in the course of IgAV. Clinical usefulness of the MPR requires further research.

Evaluation of adipokines: apelin, visfatin, and resistin in children with atopic dermatitis.

Very little is known about the role of adipokines in atopic dermatitis (AD) in children. This study aimed at analyzing the serum levels of resistin, apelin, and visfatin in children with AD in relation to body weight, AD severity, and gender. Serum concentration of adipokines was measured in 27 children with AD and in 46 healthy subjects. Selected biochemical parameters were evaluated and skin prick test was performed. Serum levels of resistin and apelin were significantly higher, whereas serum visfatin concentration was significantly lower in children with AD versus healthy controls, although an increase in resistin levels was exclusively demonstrated in boys. In AD group, a significant increase in apelin levels in girls was documented. There was no relationship between adipokines levels and the degree of allergic sensitization. Receiver operating characteristic curve analysis demonstrated that the serum apelin cutoff value differentiating children with AD from those without was >137.8 pg/mL. Resistin and visfatin cutoff values were >3.8 ng/mL and ≤ 2.13 ng/mL, respectively. Apelin and visfatin can serve as excellent indicators to distinguish children with AD from those without disease.

Dielectric Study of Liquid Crystal Dimers: Probing the Orientational Order and Molecular Interactions in Nematic and Twist-Bend Nematic Phases.

Dielectric spectroscopy in frequencies that range from 10 Hz to 1 GHz has been used to study the molecular orientational dynamics of the two types of dimers that form the twist-bend nematic phase over a wide range of temperatures for both nematic and twist-bend nematic phases. The symmetrical and asymmetrical liquid crystal dimers with the cyanobiphenyl mesogenic groups were investigated. The results were analyzed within the framework of the molecular theory of dielectric permittivity for nematogens. The two molecular processes can be assigned to the reorientation of the monomeric unit: the high frequency one to the precessional rotation of the longitudinal components of the cyanobiphenyl groups (CN) and the second (low frequency) to the end-over-end rotation of the CN dipole around the short molecular axis. The precession mode, which is determined by the local order and is almost unaffected by the phase transition from the nematic to the twist-bend phase, while the end-over-end rotation clearly slowed down at the transition, as it is affected by the growth of the intermolecular interactions. The latter corresponds well to the fact revealed by IR spectroscopy about the longitudinal correlation of the molecular dipoles.

Enantiotropic ferroelectric nematic phase in a single compound.

The ferroelectric nematic phase became the centre of interest of scientists because of its unique physical properties. The uniqueness of this particular phase results in its monotropic character in all known NF materials. Here we present the very first example of a compound with an enantiotropic ferroelectric nematic phase. Compound 3JK is complementary with already well known NF materials, i.e. RM734 and DIO and is characterized by moderately high dielectric anisotropy.

Fludarabine-Cyclophosphamide-Based Conditioning with Antithymocyte Globulin Serotherapy Is Associated with Durable Engraftment and Manageable Infections in Children with Severe Aplastic Anemia.

Severe aplastic anemia (SAA) is a bone marrow failure syndrome that can be treated with hematopoietic cell transplantation (HCT) or immunosuppressive (IS) therapy. A retrospective cohort of 56 children with SAA undergoing transplantation with fludarabine-cyclophosphamide-ATG-based conditioning (FluCyATG) was analyzed. The endpoints were overall survival (OS), event-free survival (EFS), cumulative incidence (CI) of graft versus host disease (GVHD) and CI of viral replication. Engraftment was achieved in 53/56 patients, and four patients died (two due to fungal infection, and two of neuroinfection). The median time to neutrophil engraftment was 14 days and to platelet engraftment was 16 days, and median donor chimerism was above 98%. The overall incidence of acute GVHD was 41.5%, and that of grade III-IV acute GVHD was 14.3%. Chronic GVHD was diagnosed in 14.2% of children. The probability of 2-year GVHD-free survival was 76.1%. In the univariate analysis, a higher dose of cyclophosphamide and previous IS therapy were significant risk factors for worse overall survival. Episodes of viral replication occurred in 33/56 (58.9%) patients, but did not influence OS. The main advantages of FluCyATG include early engraftment with a very high level of donor chimerism, high overall survival and a low risk of viral replication after HCT.

Cytokine production by peripheral blood CD4+ and CD8+ T cells in atopic childhood asthma.

There are conflicting studies on T cell cytokine production in childhood asthma. In this study intracellular cytokine expression of IL-2, IL-4, IL-10, IL-13, IFN-γ, and TNF-α in CD4(+) and CD8(+) T cells in children with atopic asthma were measured by flow cytometry. Results. A significant increase in the percentage of CD4(+) and CD8(+) T cells producing IL-4 and IL-13 and decrease in the percentage of CD4(+) producing IFN-γ in asthmatic children was found. The percentage of CD4(+)/IL-13(+) was significantly higher in severe asthma than in children with intermittent disease symptoms. Severity of asthma was associated with increased both serum IgE and frequencies of CD4(+)/IL-13(+) T cells, as well as duration of disease. Moreover, a decrease in FEV(1), FEV(1)/FVC was observed in relation to the severity of asthma. Changes in cytokine profile in CD8(+) subpopulation didn't depend on the severity of the disease. Conclusions. Increased production of IL-4 and IL-13 in both CD4(+) and CD8(+) T cells accompanied by decreased IFN-γ expression in CD4(+) T cells may be evidence that both lymphocyte subpopulations are implicated in the pathogenesis of asthma. Relationship of CD4(+)/IL-13(+) T cells with disease activity suggests that this lymphocyte subset may have a prominent role in childhood asthma.

Successful Salvage Treosulfan-Based Megachemotherapy With Allogeneic Stem Cell Transplantation in Nonsyndromic, Therapy-Resistant Disseminated Juvenile Xanthogranuloma: A Case Report.

Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder classified as non-Langerhans cell histiocytosis; although it is usually a benign and self-limiting disease, it can be fatal in some cases, especially with systemic dissemination. We present a case report of a boy with therapy-resistant disseminated JXG who was treated with systemic chemotherapy and received 3 allogeneic hematopoietic stem cell transplantations (allo-HSCTs) from an unrelated donor. The post-transplant period was complicated by acute graft vs host disease and lymphoproliferative disease caused by Epstein-Barr virus. Currently, almost 7.5 years after the first transplantation, the boy is in complete remission with full donor chimerism and without symptoms of JXG. The presented data confirm rare observations that allo-HSCT can lead to durable remission of systemic JXG, which warrants its use in life-threatening, therapy-resistant subtypes of disease.