1696 research outputs found
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Molekularni mehanizmi regulacije eritrocitopoeze i stres eritrocitopoeze
No full textEritrocitopoeza u bazalnim uslovima stvara nove eritrocite konstantnom brzinom. U adultnom periodu eritrocitopoeza se odvija u koštanoj srži i ima ogromni kapacitet. Regulacija ovog procesa se ostvaruje posredstvom velikog broja ćelijskih i molekularnih mehanizama koji sinergički deluju kako bi obezbedili adekvatnu oksigenaciju tkiva, a istovremeno izbegavajući probleme sa viskozitetom, povezanim sa prekomernom proizvodnjom. Stoga je ovaj proces regulisan kako mehanizmima pozitivne, tako i mehanizmima negativne povratne sprege. Za razliku od kontinuiranog obnavljanja eritrocita u bazalnim uslovima, u uslovima narušene homeostaze kao što su krvarenje, stres, inflamacija, itd, usled nemogućnosti isporuke dovoljne količine kiseonika u tkiva, dolazi do aktivacije procesa nazvanog stres eritrocitopoeza. Stres eritrocitopoeza predstavlja jedinstven proces koji se, pored koštane srži, odvija i ekstramedularno. Ekstramedularna eritrocitopoeza se, pre svega, odvija u crvenoj pulpi slezine, gde pod uticajem specifičnih signala, nastalih u njenoj mikrosredini, dolazi do nagle ekspanzije nezrelih ćelija eritroidne loze, čime se obezbeđuje adekvatan odgovor na povećane zahteve organizma za eritrocitopoezom. U ovom radu su objašnjeni osnovni molekularni mehanizmi regulacije eritrocitopoeze u bazalnim uslovima i stres eritrocitopoeze. Posebna pažnja je usmerena na zavisnost molekularnih mehanizama od mikrookruženja u kojem se ovi procesi odvijaju. Razumevanje molekularnih mehanizama koji upravljaju eritrocitopoezom i stres eritrocitopoezom od velikog je značaja za unapređenje terapijskih strategija za hematološke poremećaje
The subjective experience of transcranial electrical stimulation: a within-subject comparison of tolerability and side effects between tDCS, tACS, and otDCS
No full textLow-intensity transcranial electrical stimulation (tES), including techniques like transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and oscillatory transcranial direct current stimulation (otDCS), has been widely explored for its neuromodulatory effects on motor, cognitive, and behavioral processes. Despite well-established safety, these techniques can induce varying degrees of discomfort and side effects, potentially impacting their application. This study presents a within-subject sham-controlled experiment directly comparing the subjective experience and side effects of tDCS, tACS, and otDCS. Participants reported their discomfort levels at multiple time points during 20-min stimulation sessions and completed a side-effects questionnaire before and after each session. Results indicated that the overall discomfort levels were low across all conditions, with ≥95% reporting the absence of discomfort or mild procedure-induced discomfort. Nevertheless, tDCS and otDCS were slightly less comfortable compared to sham, especially at the beginning of stimulation, with tACS-induced discomfort levels being overall comparable to sham. The most common side / adverse effects were mild skin sensations, including itching and tingling, particularly with tDCS and otDCS, while tACS occasionally caused phosphenes and blurred vision. These findings provide a systematic comparison of tES-induced discomfort and side effects between different tES techniques, highlighting the high safety of tES, but also the importance of considering within- and between-person variability and time-course effects in tES applications
The role of inducible nitric oxide synthase in hydroxyurea impairment of angiogenesis
No full textHydroxyurea (HU) is a chemotherapeutic acting mainly through the inhibition of ribonucleotide reductase and DNA synthesis, while nitric oxide (NO) inducer/donor properties contribute significantly to its cytostatic properties. Therapeutic effects of HU are accompanied with reduction of angiogenic factors in patients with sickle cell anemia and myeloproliferative neoplasms. We have shown that HU increases inducible nitric oxide synthase (NOS2) levels and enzymatic activity. Besides endothelial nitric oxide synthase (NOS3) with a predominant role in angiogenesis, NOS2 has been also related with proangiogenic properties.The Abstract Book of European Hematology Association’s 29th Annual Congress - EHA2024 Hybrid Congress, June 13-16, Madrid, 202
The effects of multichannel ACC-targeted tDCS on decision-making in at-risk gamblers
No full textGambling is a reward-based activity that people engage in for profit or leisure. However, excessive gambling may lead
to Gambling Disorder (GD), a behavioural addiction with a rapidly growing prevalence and limited treatment options.
The evidence shows that cognitive processes which drive GD are governed by neural circuitry that could be modulated
using non-invasive brain stimulation, such as Transcranial Direct Current Stimulation (tDCS). To further explore this
possibility and gain insight into the neurocognitive mechanisms implicated in GD, we conducted a sham-controlled,
parallel-group experiment using multichannel tDCS targeting the anterior cingulate cortex (ACC), a key hub within
the decision-making and impulse-control networks. The study sampled 121 participants (61 at risk for GD and 60
control participants) who received either sham or active tDCS. Before and after the stimulation, the participants did
the Cambridge Gambling Task, a widely used measure of decision-making and risk-taking behaviours. The results
showed that gamblers demonstrated lower decision-making quality and higher impulsivity than control group.
The ACC stimulation did not affect the overall quality of decision-making or impulse control. Nevertheless, certain
aspects of risk-taking were influenced by active stimulation, depending on the specific task conditions and
participants’ characteristics. While this indicates that some facets of cognitive processes related to GD may be
affected by ACC targeted tDCS, the lack of a broader effect on more task outputs could highlight the need for more
refined outcome measures in the context of neuromodulation research to better capture the complex nuances of
gambling-related decision making and its modulation potential
Mesenchymal stromal cells in myeloid malignancies: Immunotherapeutic opportunities
Get PDFMyeloid malignancies are clonal disorders of the progenitor cells or hematopoietic stem cells, including acute myeloid leukemia, myelodysplastic syndromes, myeloproliferative malignancies, and chronic myelomonocytic leukemia. Myeloid neoplastic cells affect the proliferation and dif- ferentiation of other hematopoietic lineages in the bone marrow and peripheral blood, leading to severe and life-threatening complications. Mesenchymal stromal cells (MSCs) residing in the bone marrow exert immunosuppressive functions by suppressing innate and adaptive immune systems, thus creating a supportive and tolerant microenvironment for myeloid malignancy progression. This review summarizes the significant features of MSCs in myeloid malignancies, including their role in regulating cell growth, cell death, and antineoplastic resistance, in addition to their immunosuppressive contributions. Understanding the implications of MSCs in myeloid malig- nancies could pave the path for potential use in immunotherapy
Current opinions and practices in post-stroke movement disorders: Survey of movement disorders society members
No full textBackground: Post-stroke movement disorders (PSMD) encompass a wide array of presentations, which vary in mode of onset, phenomenology, response to treatment, and natural history. There are no evidence-based guidelines on the diagnosis and treatment of PSMD. Objectives: To survey current opinions and practices on the diagnosis and treatment of PSMD. Methods: A survey was developed by the PSMD Study Group, commissioned by the International Parkinson's and Movement Disorders Society (MDS). The survey, distributed to all members, yielded a total of 529 responses, 395 (74.7%) of which came from clinicians with experience with PSMD. Results: Parkinsonism (68%), hemiballismus/hemichorea (61%), tremor (58%), and dystonia (54%) were by far the most commonly endorsed presentation of PSMD, although this varied by region. Basal ganglia stroke (76% of responders), symptoms contralateral to stroke (75%), and a temporal relationship (59%) were considered important factors for the diagnosis of PSMD. Oral medication use depended on the phenomenology of the PSMD. Almost 50% of respondents considered deep brain stimulation and ablative surgeries as options for treatment. The lack of guidelines for the diagnosis and treatment was considered the most important gap to address. Conclusions: Regionally varying opinions and practices on PSMD highlight gaps in (and mistranslation of) epidemiologic and therapeutic knowledge. Multicenter registries and prospective community-based studies are needed for the creation of evidence-based guidelines to inform the diagnosis and treatment of patients with PSMD
Exploring the Link between Hydrodynamic Size and Immunoglobulins of Circulating Immune Complexes in Rheumatoid Arthritis Patients
Get PDFThe function of immune complexes in rheumatoid arthritis (RA) is related to their composition and size. Using dynamic light scattering (DLS), we investigated the link between the RA circulating immune complex (CIC) particles’ size and the CIC immunoglobulin level. In this study, 30 RA patients and 30 healthy individuals were included. IgA, IgG, and IgM were found in all analyzed CICs, but more IgA and IgG were found in RA than in control CICs. In both control and RA CICs, DLS detected 50 particles that differed in size and clustered around two size groups: with a 7.5–164 nm radius and with a 342–1718 nm radius. An increased level of IgA in RA CICs, compared to control ones, was associated with more than 50% of CIC particles. In RA, compared to the control, a higher number of CICs with 28.2 nm, 531 nm, 712 nm, and 1718 nm particles and a lower number of CICs with 78.8 nm particles were detected. This particle distribution pattern did not reflect the changes in the CIC immunoglobulin level. Thus, RA elevated CIC IgA was linked with all these particles (except the 1718 nm particle), the IgM increase was linked with 43.8 nm and 712 nm particles, and the IgG increase was linked with the 712 nm particle only. This study provides the very first data on the association between CIC particles’ size, CIC immunoglobulin level, and RA. It opens the possibility that the size of CICs determined by DLS can be used as a criterion in RA diagnosis or monitoring after a large-scale study confirmation
TMG Symmetry and Kinematic Analysis of the Impact of Different Plyometric Programs on Female Athletes’ Lower-Body Muscles
No full textAsymmetries in sports are common and can lead to various issues; however, different training programs can facilitate change. This study aimed to assess the effects of opposing plyometric programs on tensiomyography lateral symmetry (TMG LS)/inter-limb asymmetry in female athletes’ lower-body muscles, alongside kinematic and body composition parameters. Twenty female subjects from basketball, volleyball, and track and field (sprinting disciplines) were divided into two experimental groups (n = 10 each). Two six-week plyometric programs (two sessions/week) were implemented: the first program (E1) focused on eccentric exercises, depth landings, while the second (E2) emphasized concentric exercises, squat jumps. TMG assessed LS in six muscles: vastus lateralis, vastus medialis, biceps femoris, semitendinosus, gastrocnemius lateralis, and gastrocnemius medialis. A kinematic analysis of the countermovement jump (CMJ) and body composition was conducted using “Kinovea; Version 0.9.4” software and InBody 770, respectively. The results showed significant increases in LS percentages (E1—VL 9.9%, BF 18.0%, GM 10.6% and E2—BF 22.5%, p < 0.05), and a significant large effect in E1 for VL, and in E2 for BF, p < 0.01). They also showed that E1 had a significant effect on VL, and that E2 had a significant large effect on BF (p < 0.01). E1 also led to increased lean muscle mass in both legs (left: 1.88%, right: 2.74%) and decreased BMIs (−0.4, p < 0.05). Both programs improved LS, with E1 enhancing muscle mass and lower-body positioning in CMJ. We recommend future studies use varied jump tests, incorporate 3D kinematic analysis, include male subjects, and examine more muscles to enhance TMG LS analysis
Increased levels of fibrinogen and tissue factor are biomarkers of thrombosis in patients with multiple myeloma
No full textBackground:Inflammation plays a pivotal role in multiple myeloma (MM) progression and thrombotic events. This procoagulant shift is
supported by a complex interplay involving inflammatory cytokines, adhesion molecules, and the activation of coagulation
factors.
Aims:Besides examination of laboratory and clinical parameters, the study is aimed to define interplay between inflammation and
coagulation factors for thrombus formation in patients with MM.The Abstract Book of European Hematology Association’s 29th Annual Congress - EHA2024 Hybrid Congress, June 13-16, Madrid, 202
Bone Marrow Adipose Tissue: Impacts on Bone Marrow Stem Cell Niche and Hematopoietic System
No full textBone marrow adipose tissue (BMAT) is a strong orchestrator of the bone marrow microenvironment (BME), bone regeneration and hematopoiesis, but also energy homeostasis and endocrine signaling. Although imposed by its anatomical site, nutritional state or aging, endocrine and metabolic roles of BMAT can overcome BME. The role of BMAT is strongly dependent on marrow and skeletal health, and whether this relationship is causal is still under investigation. Here, we summarized findings indicating an important reprogramming, regulatory and even prognostic role of BMAT in different hematologic malignancies, including myelodysplastic syndrome (MDS), leukemias and multiple myeloma. Bone marrow adipogenesis is an emergency phenomenon that produces hematopoietic stem and progenitor cell (HSPC) niche factors, where accumulation of bone marrow adipocytes (BMAds) may provide selective advantage to specific pre-leukemic HSPCs and clonal hematopoiesis. Lipid status and metabolic changes in BME dictate the outcome of bidirectional crosstalk between BMAds and HSPCs. Lipolysis induced by the presence of leukemic (neoplastic) cells leads to metabolic reprogramming in BMAds, dedifferentiation and potentially to generation of so-called, cancer-associated adipocytes or even fibroblasts. On the other hand, BMAd-released fatty acids, extracellular vesicles, growth factors and lncRNA can trigger survival mechanisms in malignant hematopoietic cells, also modifying their drug response. Collectively, we can assume that revealing of BMAT-associated factors that regulate (neoplastic) hematopoietic process can contribute to the novel strategies for improvement of adult hematological system in aging and malignancy