Realistic total-body J-PET geometry optimization: Monte Carlo study.

Background: Total-body (TB) Positron Emission Tomography (PET) is one of the most promising medical diagnostics modalities, opening new perspectives for personalized medicine, low-dose imaging, multi-organ dynamic imaging or kinetic modeling. The high sensitivity provided by total-body technology can be advantageous for novel tomography methods like positronium imaging, demanding the registration of triple coincidences. Currently, state-of-the-art PET scanners use inorganic scintillators.

Topical siRNA therapy of diabetic-like wound healing.

Non-healing wounds are a serious complication in diabetic patients. One of the detrimental factors contributing to limited wound healing is the accumulation of metalloproteinase-9 (MMP-9) in the wound. Selective inhibition of MMP-9 is one of the established therapeutic targets for diabetic wound healing.

Multifunctional, Fluorene-Based Modulator of Cholinergic and GABAergic Neurotransmission as a Novel Drug Candidate for Palliative Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss and behavioral and psychological symptoms of dementia (BPSD). Given that cholinergic neurons are predominantly affected in AD, current treatments primarily aim to enhance cholinergic neurotransmission. However, imbalances in other neurotransmitters, such as γ-aminobutyric acid (GABA), also contribute to AD symptomatology.

Discovery of New Highly Potent Histamine H Receptor Antagonists, Calcium Channel Blockers, and Acetylcholinesterase Inhibitors.

At present, one of the most promising strategies to tackle the complex challenges posed by Alzheimer's disease (AD) involves the development of novel multitarget-directed ligands (MTDLs). To this end, we designed and synthesized nine new MTDLs using a straightforward and cost-efficient one-pot Biginelli three-component reaction. Among these newly developed compounds, one particular small molecule, named has emerged as a promising MTDL.

Exploring Novel GSK-3β Inhibitors for Anti-Neuroinflammatory and Neuroprotective Effects: Synthesis, Crystallography, Computational Analysis, and Biological Evaluation.

In the pathogenesis of Alzheimer's disease, the overexpression of glycogen synthase kinase-3β (GSK-3β) stands out due to its multifaced nature, as it contributes to the promotion of amyloid β and tau protein accumulation, as well as neuroinflammatory processes. Therefore, in the present study, we have designed, synthesized, and evaluated a new series of GSK-3β inhibitors based on the -(pyridin-2-yl)cyclopropanecarboxamide scaffold. We identified compound , demonstrating an IC of 70 nM against GSK-3β.

Connecting GSK-3β Inhibitory Activity with IKK-β or ROCK-1 Inhibition to Target Tau Aggregation and Neuroinflammation in Alzheimer's Disease-Discovery, In Vitro and In Cellulo Activity of Thiazole-Based Inhibitors.

GSK-3β, IKK-β, and ROCK-1 kinases are implicated in the pathomechanism of Alzheimer's disease due to their involvement in the misfolding and accumulation of amyloid β (Aβ) and tau proteins, as well as inflammatory processes. Among these kinases, GSK-3β plays the most crucial role. In this study, we present compound , a novel, remarkably potent, competitive GSK-3β inhibitor (IC = 8 nM, K = 2 nM) that also exhibits additional ROCK-1 inhibitory activity (IC = 2.

Elevated periodic limb movement index is associated with hypoxemia in children with early onset scoliosis.

Purpose: Patients with early onset scoliosis are at high risk of sleep disordered breathing, sleep disruption, and adverse consequences of poor sleep. In this study, we aim to assess the prevalence of periodic limb movements of sleep in a cohort of children with early onset scoliosis and identify factors that correlate with the presence of periodic limb movements.

Methods: This is a retrospective chart review of 40 patients with EOS (ages 1-17 years) who underwent a PSG from 2003 through 2019.

Feasibility of the J-PET to monitor the range of therapeutic proton beams.

Purpose: The aim of this work is to investigate the feasibility of the Jagiellonian Positron Emission Tomography (J-PET) scanner for intra-treatment proton beam range monitoring.

Methods: The Monte Carlo simulation studies with GATE and PET image reconstruction with CASToR were performed in order to compare six J-PET scanner geometries. We simulated proton irradiation of a PMMA phantom with a Single Pencil Beam (SPB) and Spread-Out Bragg Peak (SOBP) of various ranges.

Multifunctional agents against Alzheimer's disease based on oxidative stress: Polysubstituted pyrazine derivatives synthesized by multicomponent reactions.

As Alzheimer's disease (AD) is a neurodegenerative disease with a complex pathogenesis, the exploration of multi-target drugs may be an effective strategy for AD treatment. Multifunctional small molecular agents can be obtained by connecting two or more active drugs or privileged pharmacophores by multicomponent reactions (MCRs). In this paper, two series of polysubstituted pyrazine derivatives with multifunctional moieties were designed as anti-AD agents and synthesized by Passerini-3CR and Ugi-4CR.

Discovery of novel multifunctional ligands targeting GABA transporters, butyrylcholinesterase, β-secretase, and amyloid β aggregation as potential treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a global health problem in the medical sector that will increase over time. The limited treatment of AD leads to the search for a new clinical candidate. Considering the multifactorial nature of AD, a strategy targeting number of regulatory proteins involved in the development of the disease is an effective approach.

Comparative studies of the sensitivities of sparse and full geometries of Total-Body PET scanners built from crystals and plastic scintillators.

Background: Alongside the benefits of Total-Body imaging modalities, such as higher sensitivity, single-bed position, low dose imaging, etc., their final construction cost prevents worldwide utilization. The main aim of this study is to present a simulation-based comparison of the sensitivities of existing and currently developed tomographs to introduce a cost-efficient solution for constructing a Total-Body PET scanner based on plastic scintillators.

Phosphorylation of tyrosine 90 in SH3 domain is a new regulatory switch controlling Src kinase.

The activation of Src kinase in cells is strictly controlled by intramolecular inhibitory interactions mediated by SH3 and SH2 domains. They impose structural constraints on the kinase domain holding it in a catalytically non-permissive state. The transition between inactive and active conformation is known to be largely regulated by the phosphorylation state of key tyrosines 416 and 527.

Structure-Guided Design of -Methylpropargylamino-Quinazoline Derivatives as Multipotent Agents for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a complex disease with an unknown etiology. Available treatments, limited to cholinesterase inhibitors and -methyl-d-aspartate receptor (NMDAR) antagonists, provide symptomatic relief only. As single-target therapies have not proven effective, rational specific-targeted combination into a single molecule represents a more promising approach for treating AD, and is expected to yield greater benefits in alleviating symptoms and slowing disease progression.

Detection of range shifts in proton beam therapy using the J-PET scanner: a patient simulation study.

The Jagiellonian PET (J-PET) technology, based on plastic scintillators, has been proposed as a cost effective tool for detecting range deviations during proton therapy. This study investigates the feasibility of using J-PET for range monitoring by means of a detailed Monte Carlo simulation study of 95 patients who underwent proton therapy at the Cyclotron Centre Bronowice (CCB) in Krakow, Poland. Approach: Discrepancies between prescribed and delivered treatments were artificially introduced in the simulations by means of shifts in patient positioning and in the Hounsfield unit to the relative proton stopping power calibration curve.

Cerebral Projection of Mirrored Touch via sLORETA Imaging.

Touch is one of the primary communication tools. Interestingly, the sensation of touch can also be experienced when observed in another person. Due to the system of mirror neurons, it is, in fact, being mapped on the somatosensory cortex of the observer.

Novel drug-like fluorenyl derivatives as selective butyrylcholinesterase and β-amyloid inhibitors for the treatment of Alzheimer's disease.

Butyrylcholinesterase (BuChE) and amyloid β (Aβ) aggregation remain important biological target and mechanism in the search for effective treatment of Alzheimer's disease. Simultaneous inhibition thereof by the application of multifunctional agents may lead to improvement in terms of symptoms and causes of the disease. Here, we present the rational design, synthesis, biological evaluation and molecular modelling studies of novel series of fluorene-based BuChE and Aβ inhibitors with drug-like characteristics and advantageous Central Nervous System Multiparameter Optimization scores.

Efficiency determination of J-PET: first plastic scintillators-based PET scanner.

Background: The Jagiellonian Positron Emission Tomograph is the 3-layer prototype of the first scanner based on plastic scintillators, consisting of 192 half-metre-long strips with readouts at both ends. Compared to crystal-based detectors, plastic scintillators are several times cheaper and could be considered as a more economical alternative to crystal scintillators in future PETs. JPET is also a first multi-photon PET prototype.

Discovery of new, highly potent and selective inhibitors of BuChE - design, synthesis, in vitro and in vivo evaluation and crystallography studies.

The symptomatic and disease-modifying effects of butyrylcholinesterase (BuChE) inhibitors provide an encouraging premise for researching effective treatments for Alzheimer's disease. Here, we examined a series of compounds with a new chemical scaffold based on 3-(cyclohexylmethyl)amino-2-hydroxypropyl, and we identified a highly selective hBuChE inhibitor (29). Based on extensive in vitro and in vivo evaluations of the compound and its enantiomers, (R)-29 was identified as a promising candidate for further development.

Effect of Mental Task on Sex Differences in Muscle Fatigability: A Review.

Previous research demonstrated that there are observable sex differences in developing muscle fatigue when mental task during fatiguing activity is present; however, there is no available review on this matter. Therefore, this review aimed to summarize the findings of previous studies investigating the effect of mental task on muscle fatigue in men and women. To conduct the review, we utilized searches using the electronic databases Web of Science, PubMed, Scopus, and EBSCO Cinahl Ultimate.

ProTheRaMon - a GATE simulation framework for proton therapy range monitoring using PET imaging.

Objective: This paper reports on the implementation and shows examples of the use of the ProTheRaMon framework for simulating the delivery of proton therapy treatment plans and range monitoring using positron emission tomography (PET). ProTheRaMon offers complete processing of proton therapy treatment plans, patient CT geometries, and intra-treatment PET imaging, taking into account therapy and imaging coordinate systems and activity decay during the PET imaging protocol specific to a given proton therapy facility. We present the ProTheRaMon framework and illustrate its potential use case and data processing steps for a patient treated at the Cyclotron Centre Bronowice (CCB) proton therapy center in Krakow, Poland.

Onset Timing of Hyoid Muscles Activation during Cervical Flexion Is Position-Dependent: An EMG Study.

Due to the high prevalence of neck pain, considerable attention is paid to the function of cervical flexor muscles. Although the deep and superficial cervical flexor muscles have been evaluated, the impact of hyoid muscles on cervical flexion is still not well known. We, therefore, aimed to investigate the activation of hyoid muscles during physiological cervical flexion, and to determine the impact of different starting positions on cervical flexion muscle activation.

Micro-computed tomography for analysis of heavy metal accumulation in the opercula.

Micro-computed tomography (micro-CT) provides numerous opportunities in biomedical research. It allows the examination of samples in a non-destructive manner and visualization of the inner structures of various biological and nonbiological objects. This study was conducted to evaluate the potential of micro-CT scanner in the assessment of heavy metal accumulation in the opercula.

The Effects of Elastic Band Exercises with PNF on Shooting Speed and Accuracy in Ball Hockey Players during the COVID-19 Pandemic.

The coronavirus pandemic has affected life and left one of the strongest negative effects on sport. The aim of our study was to evaluate how a simple exercise performed with elastic resistance during the COVID-19 pandemic, when athletes cannot train, affects the basic shooting characteristics of ball hockey players. Extra-league ball hockey players ( = 30, age 19-37 years) were randomly divided into an experimental group, which performed elastic resistance exercises with Proprioceptive Neuromuscular Facilitation (PNF) elements for eight weeks, and a control group, which did not perform any exercises.

Obstructive Apnea and Hypopnea Length in Normal Children and Adolescents.

(1) Background: Breathing is an essential function that requires both metabolic (or au-tomatic) and voluntary (behavioral) control during wakefulness but during sleep depends on metabolic control via peripheral and central chemoreceptors. Breathing during sleep disordered breathing also depends on the maturity of the neural centers and the strength of the respiratory muscles. We do not know if the response to apnea varies with age.

Discovery of 1-(phenylsulfonyl)-1H-indole-based multifunctional ligands targeting cholinesterases and 5-HT receptor with anti-aggregation properties against amyloid-beta and tau.

Multifunctional ligands as an essential variant of polypharmacology are promising candidates for the treatment of multi-factorial diseases like Alzheimer's disease. Based on clinical evidence and following the paradigm of multifunctional ligands we have rationally designed and synthesized a series of compounds targeting processes involved in the development of the disease. The biological evaluation led to the discovery of two compounds with favorable pharmacological characteristics and ADMET profile.