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.

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.

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.

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.

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.

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.

Successful Allogeneic Stem Cell Transplantation in Nuclear Factor-Kappa B Essential Modulator Deficiency Syndrome After Treosulfan-Based Conditioning: A Case Report.

BACKGROUND: X-linked EDA-ID1 (ectodermal dysplasia, anhidrotic, with immunodeficiency 1, Online Mendelian Inheritance in Man [OMIM] 300291), or NEMO (nuclear factor kappa B essential modulator) deficiency syndrome, is caused by mutations in the IKBKG/NEMO gene. We report the case of a boy with EDA-ID1 who underwent allogeneic stem cell transplantation. METHODS: In early infancy, the patient developed an atypical, severe, initial manifestation resembling Omenn syndrome with infections, and he underwent allogeneic stem cell transplantation from an unrelated 9 of 10 HLA matched donor with a mismatch in the DQB1 allele after conditioning with treosulfan, fludarabine, thiotepa, and antithymocyte globulin (Grafalon). The post-transplant period was complicated by cytomegalovirus replication and mild, grade 2 graft vs host disease. Because of NEMO deficiency syndrome-associated enteropathy and continuous weight loss, parenteral nutrition was started and the patient was fed an elemental formula and a gluten-free diet. Over a period of 3 years, the patient had 7 incidents of blood stream infections caused by Staphylococci or gut-derived Gram-negative flora, with 1 incident of septic shock caused by Escherichia coli. The blood stream infection stopped after gastrointestinal tract decontamination was done once per month for 7-day courses alternately with rifaximin, vancomycin, and gentamicin sulfate. CONCLUSIONS: Patients with NEMO deficiency syndrome require very complex, multidisciplinary care, and immunodeficiency correction can only be observed as one of the critical points in patient care. Developmental problems, enteropathy with the need for intravenous hyperalimentation, and specific interventions for other clinical manifestations of multifaceted syndrome are needed for proper care.

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.

Familial Celiac Disease Remission as a Result of a Full Donor Immunologic Recovery After Sibling Cord Blood Transplantation for Chronic Granulomatous Disease: A Case Report.

We present a case report of a boy diagnosed with both chronic granulomatous disease (CGD) and familial celiac disease (CD) who underwent cord blood transplantation from a partially matched sibling donor. The presentation of CD resembled Crohn-like enteropathy, which is a canonical manifestation of CGD. Nearly 1 year post-hematopoietic stem cell transplantation (HSCT), a gluten-containing diet was reintroduced, and no reappearance of clinical, serologic, or histologic markers of CD was observed. The relatively high incidence of rare genetic diseases in pediatric patients suggests the need for additional caution in the interpretation of symptoms mimicking already known hallmarks of more common conditions. In addition, the presented data confirm the previous rare observations that allogeneic HSCT leads to durable induction of gluten tolerance in patients with CD, which can warrant its use in patients with refractory subtypes of CD.

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.

Imatinib in the treatment of chronic myeloid leukemia in children and adolescents is effective and well tolerated: Report of the Polish Pediatric Study Group for the Treatment of Leukemias and Lymphomas.

BACKGROUND: Chronic myeloid leukemia (CML) constitutes only 2-3% of all leukemias in pediatric patients. Philapelphia chromosome and BCR-ABL fusion are genetic hallmarks of CML, and their presence is crucial for targeted molecular therapy with tyrosine kinase inhibitors (TKIs), which replaced hematopoietic stem cell transplantation (HSCT) as a standard first-line therapy. The disease in pediatric population is rare, and despite molecular and clinical similarities to CML in adults, different approach is needed, due to the long lifetime expectancy and distinct developmental characteristics of affected children. OBJECTIVES: The objective of this study is to evaluate treatment with imatinib in Polish pediatric patients with CML. MATERIAL AND METHODS: We analyzed the results of treatment with imatinib in 57 pediatric patients (June 2006 - January 2016) from 14 Polish pediatric hematology and oncology centers. RESULTS: In the study group, 40 patients continued imatinib (median follow-up: 23.4 months), while in 17 the treatment was terminated (median follow-up: 15.1 months) due to therapy failure. In the latter group, 13 patients underwent HSCT, while 4 switched to second-generation TKIs. The 5-year overall survival rate (OS) in the study group was 96%, and the 5-year event-free survival (EFS) was 81%. CONCLUSIONS: Our results confirm that the introduction of TKI therapy has revolutionized the treatment of CML in the pediatric population by replacing the previous method of treatment with HSCT and allowing a high percentage of OS and EFS.

Evaluation of adipokines in children with cystic fibrosis.

INTRODUCTION: Patients with CF present numerous pathological conditions such as malnutrition, depletion of fat-free mass, metabolic disturbances (abnormal glucose metabolism, increased insulin resistance, chronic energy deficit, local and chronic inflammation), which could affect or be associated with altered adipokines concentration Material and Methods: We aimed in this study to investigate the levels of selected adipokines such as resistin, apelin, adiponectin to demonstrate their application as possible markers of inflammation. RESULTS: Serum level of resistin was higher (p < 0.001) and adiponectin - lower (p=0.02) in CF children than in healthy children. There was no difference in serum apelin level between two examined groups. However, values of adiponectin/BMI and apelin/BMI ratios in CF did not differ significantly from controls. Higher values of resistin/BMI ratio in CF in comparison to controls were observed Serum resistin/adiponectin ratio was significantly higher in CF patients than in controls (p < 0.0001). Resistin/BMI ratio correlated negatively with FEV1 (R:-48,p < 0.043). Serum resistin/adiponectin ratio correlated negatively with FEV1/FVC (R:-49, p=0.04), Adipokines showed no correlation with BMI and BMI-SDS, glucose, total cholesterol, and LDL-, HDL-cholesterol, triglyceride serum levels. Spirometric parameters FEV1, FVC, VC correlated negatively with serum glucose levels (R: -0.55, p < 0.018; R: -0.65 p < 0.0025; R:-0.76, p < 0.0008 respectively). FEV1 and FVC correlated positively with BMI-SDS (R:0.58, p < 0.01; R:0.5, p < 0.036, respectively). CONCLUSIONS: A significant increase in resistin concentration expressed also as resistin/BMI, and resistin/adiponectin ratios, observed in children with CF may suggests that this adipokine is involved in the inflammatory process underlying the disease and is related to worse spirometric parameters describing airways obstruction.

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.

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.

Effect of intrauterine infection and perinatal risk factors on serum concentrations of insulin like growth factor (IGF-I) in full-term and preterm newborns.

OBJECTIVES: IGF-I is believed to be a key factor in fetal growth dynamics It is widely known, that serious early-onset infection in the newborn is a risk factor for further developmental disturbances in a child. However, effect of congenital infection as well as an influence of infectious and non-infectious perinatal risk factors on circulating IGF-I concentrations in newborns has not been examined, yet. DESIGN: Thus, the aim of this study was: 1) evaluation of IGF-I venous blood serum concentration in full-term and premature infants considering their sex, occurrence of intrauterine infection and perinatal risk factors; 2) establishing the relationship between IGF-I serum concentrations and chosen anthropometric parameters values in infected and healthy newborns. SETTING: The study involved 112 newborns appropriate for gestational age. Taking into consideration occurrence of early onset infection and gestational age we divided examined children into 4 groups: I group--infected, full-term newborns; II group--infected premature newborns; III group--healthy full-term newborns; IV group--healthy premature newborns. In all infants immediately after birth anthropometric measurements were performed (birth weight, body length, circumference of head and circumference of chest) and serum IGF-I concentration was determined. RESULTS: We demonstrated that full-term infants with intrauterine infection have statistically significantly higher concentration of IGF-I in blood serum than infected premature infants and healthy full-term infants. Analysis of correlation revealed a significant positive linear correlations between IGF-I serum concentration and gestational age and anthropometric parameters values. CONCLUSIONS: We conclude that intrauterine infection increases serum IGF-I concentration in full-term infants, but not in preterm infants, that may be a result of immaturity. We suggest serum IGF-I concentration may be considered an additional element of developmental and nutritional state assessment in infected newborn.

Concomitant EBV-related B-cell proliferation and juvenile myelomonocytic leukemia in a 2-year-old child.

We present a case of a 2-year-old girl, who developed concomitant EBV-related B-cell proliferation and juvenile myelomonocytic leukemia (JMML). JMML was initially not recognized because of predominant B-cell proliferation. The activating N-RAS mutation was retrospectively already detectable at this early stage. Our findings support the hypothesis that EBV may contribute to JMML pathogenesis by stimulating pre-existing malignant clones. However, such stimulation of leukemic clone does not require the direct incorporation of the virus into myeloid progenitors. Most probably a cytokine burst resulting from EBV infection allows expansion of pre-existing malignant myeloid progenitors. Further studies are required to delineate exact mechanisms of EBV-related promotion of the JMML clone.

[Periodic fever, aphtosus stomatitis, pharyngitis, cervical adenopathy syndrome (PFAPA syndrome) in 4-years old girl--case report]. / Zespól okresowej goraczki, aftowego zapalenia jamy ustnej, zapalenia gardla oraz limfadenopatii szyjnej (PFAPA) u 4-letniej dziewczynki--opis przypadku.

Characteristic feature of PFAPA syndrome is periodic episodes of fever recurring in 21-28 days in infants and young children. Fever is accompanied by aphtosus stomatitis, pharyngitis and cervical adenopathy. Diagnosis of this syndrome are based on typical clinical manifestations, because there are no characteristic changes in laboratory findings. The reason of this syndrome is unknown. We described a case of 4 years old girl with typical manifestations of this syndrome. We excluded others reasons of periodic fever. PFAPA syndrome passed after 2 years of duration after adenothomy.