Advancing the Clinical and Molecular Understanding of Cornelia de Lange Syndrome: A Multidisciplinary Pediatric Case Series and Review of the Literature.

Cornelia de Lange syndrome (CdLS) is a complex genetic disorder with distinct facial features, growth limitations, and limb anomalies. Its broad clinical spectrum presents significant challenges in pediatric diagnosis and management. Due to cohesin complex mutations, the disorder's variable presentation requires extensive research to refine care and improve outcomes. This article provides a case series review of pediatric CdLS patients alongside a comprehensive literature review, exploring clinical variability and the relationship between genotypic changes and phenotypic outcomes. It also discusses the evolution of diagnostic and therapeutic techniques, emphasizing innovations in genetic testing, including detecting mosaicism and novel genetic variations. The aim is to synthesize case studies with current research to advance our understanding of CdLS and the effectiveness of management strategies in pediatric healthcare. This work highlights the need for an integrated, evidence-based approach to diagnosis and treatment. It aims to fill existing research gaps and advocate for holistic care protocols and tailored treatment plans for CdLS patients, ultimately improving their quality of life.

CAR-T Cell Therapy in the Treatment of Pediatric Non-Hodgkin Lymphoma.

Non-Hodgkin lymphomas (NHL) are a group of cancers that originate in the lymphatic system, especially from progenitor or mature B-cells, T-cells, or natural killer (NK) cells. NHL is the most common hematological malignancy worldwide and also the fourth most frequent type of cancer among pediatric patients. This cancer can occur in children of any age, but it is quite rare under the age of 5 years. In recent decades, available medicines and therapies have significantly improved the prognosis of patients with this cancer. However, some cases of NHL are treatment resistant. For this reason, immunotherapy, as a more targeted and personalized treatment strategy, is becoming increasingly important in the treatment of NHL in pediatric patients. The objective of the following review is to gather the latest available research results, conducted among pediatric and/or adult patients with NHL, regarding one immunotherapy method, i.e., chimeric antigen receptor (CAR) T cell therapy. We focus on assessing the effectiveness of CAR-T cell therapy, which mainly targets B cell markers, CD19, CD20, and CD22, their connections with one another, sequential treatment, or connections with co-stimulatory molecules. In addition, we also evaluate the safety, aftermath (especially neurotoxicities) and limitations of CAR-T cell therapy.

Esketamine and Psilocybin-The Comparison of Two Mind-Altering Agents in Depression Treatment: Systematic Review.

This publication discusses two compounds belonging to the psychoactive substances group which are studied in the context of depression treatment-psilocybin and esketamine. The former is a naturally occurring psychedelic. The latter was invented in the laboratory exactly 60 years ago. Although the substances were controversial in the past, recent studies indicate the potential of those substances as novel antidepressant agents. The PubMed/MEDLINE database was used to identify articles for systematic review, using the following search terms: (depression) AND (psilocybin) OR (ketamine). From 617 items, only 12 articles were obtained in the final analyses. Three articles were devoted to psilocybin in depression treatment and nine to esketamine. In most studies, esketamine showed a significant reduction in both depressive symptoms and suicidal ideation shortly after intake and after a month of treatment compared to baseline and to standard-of-care antidepressant agents. Psilocybin's antidepressive effects occurred one day after intake and after 6-7 weeks of treatment and were maintained for up to 6 or 8 months of follow-up. One study indicated that psilocybin's effects are comparable with and may be superior to escitalopram treatment. Both esketamine and psilocybin demonstrated rapid and long-term effects in reducing depression symptoms and, after overcoming some limitations, may be considered as novel antidepressant agents in future.

The Potential Role of Serotonergic Hallucinogens in Depression Treatment.

Due to an increasing number of depression diagnoses and limited effective treatments, researchers continue to explore novel therapeutic strategies for this disorder. Recently, interest has revolved around the use of serotonergic psychedelics to reduce the symptoms of depression. In this systematic review, we summarize the currently available knowledge on the safety and efficacy of psychedelic substances for the treatment of depression. A literature search of the PubMed/MEDLINE database identified 14 clinical trials from the last 10 years that examined the use of psilocybin, MDMA, DMT, or LSD for the treatment of depression symptoms. Some psychedelics, especially psilocybin, demonstrated an ability to reduce depressive symptoms as measured by several psychological scales, which was often sustained for months after the last psychedelic session. Moreover, one study revealed that psilocybin has comparable efficacy to escitalopram in the treatment of depression. None of the studies reported any serious adverse events associated with psychedelic administration. The reviewed studies suggest that psychedelics have great potential in depression therapy and, after addressing and overcoming the current study limitations, may be used as a novel method of treating depression in the future.

Comparative PIV and LDA studies of Newtonian and non-Newtonian flows in an agitated tank.

The paper presents results of an experimental study of the fluid velocity field in a stirred tank equipped with a Prochem Maxflo T (PMT) type impeller which was rotating at a constant frequency of N = 4.1 or 8.2 s-1 inducing transitional (Re = 499 or 1307) or turbulent (Re = 2.43 × 104) flow of the fluid. The experiments were performed for a Newtonian fluid (water) and a non-Newtonian fluid (0.2 wt% aqueous solution of carboxymethyl cellulose, CMC) exhibiting mild viscoelastic properties. Measurements were carried out using laser light scattering on tracer particles which follow the flow (2-D PIV). For both the water and the CMC solution one primary and two secondary circulation loops were observed within the fluid volume; however, the secondary loops were characterized by much lower intensity. The applied PMT-type impeller produced in the Newtonian fluid an axial primary flow, whilst in the non-Newtonian fluid the flow was more radial. The results obtained in the form of the local mean velocity components were in satisfactory agreement with the literature data from LDA. Distribution of the shear rate in the studied system was also analyzed. For the non-Newtonian fluid an area was computed where the elastic force dominates over the viscous one. The area was nearly matching the region occupied by the primary circulation loop.

Simulation of immiscible liquid-liquid flows in complex microchannel geometries using a front-tracking scheme.

The three-dimensional two-phase flow dynamics inside a microfluidic device of complex geometry is simulated using a parallel, hybrid front-tracking/level-set solver. The numerical framework employed circumvents numerous meshing issues normally associated with constructing complex geometries within typical computational fluid dynamics packages. The device considered in the present work is constructed via a module that defines solid objects by means of a static distance function. The construction combines primitive objects, such as a cylinder, a plane, and a torus, for instance, using simple geometrical operations. The numerical solutions predicted encompass dripping and jetting, and transitions in flow patterns are observed featuring the formation of drops, 'pancakes', plugs, and jets, over a wide range of flow rate ratios. We demonstrate the fact that vortex formation accompanies the development of certain flow patterns, and elucidate its role in their underlying mechanisms. Experimental visualisation with a high-speed imaging are also carried out. The numerical predictions are in excellent agreement with the experimental data.

Bulk advection and interfacial flows in the binary coalescence of surfactant-laden and surfactant-free drops.

This work focuses on the study of bulk flows accompanying the coalescence of two aqueous drops, one containing surfactant and the other surfactant-free, in silicone oils of various viscosities. It is observed that the surfactant-free drop intrudes into the surfactant-laden drop in the form of a penetrating jet whose speed increases and average radius decreases with increasing outer phase viscosity. Mixing patterns within the coalescing drops are due to the force imbalance caused by capillary pressure difference and surfactant-induced Marangoni stresses. The driving force for mixing associated with the difference in interfacial tension between the drops is considerably stronger than that related to the drop size. The long timescale mixing of the drops is driven by rapid interior convection, and the subsequent, slow, diffusive process. Three-dimensional numerical simulations show excellent qualitative and quantitative agreement with the experimental results. The implications of our results to formulation strategies of complex microstructures in practical applications are also discussed.

Effect of Soluble Surfactants on the Kinetics of Thinning of Liquid Bridges during Drops Formation and on Size of Satellite Droplets.

The results of an experimental study on thinning and breakage of liquid bridges during detachment of a drop from the tip of a capillary are presented for a series of surfactant solutions (including cationic, anionic, and nonionic surfactants) over a broad range of molecular masses, values of critical micelle concentration, and concentrations. The used experimental protocol revealed that the kinetics of the bridge thinning depends much more on the dynamics of adsorption at the surface of the drop before it destabilizes, rather than on the depletion of surfactant from the surface of the thinning bridge due to its stretching as the instability develops. The kinetics of the bridge thinning and the size of satellite droplets formed after the bridge breakage depend considerably on the surfactant concentration and the value of critical micelle concentration. It is proposed that the dynamic surface tension on the time scale of the drop formation can be used as an effective surface tension for the description of the bridge kinetics over the broad range of experimental conditions used.