The sacroiliac joint (SIJ) exhibits significant variation in auricular surface morphology. This variation influences the mechanics of the SIJ, a central node for transmitting mechanical energy from upper body to lower limbs and vice versa. The impact of the auricular surface morphology on stress and deformation in the SIJ remains poorly understood to date. Computed tomography scans obtained from 281 individuals were included to extract the geometry of the pelvic ring. Then, the auricular surface area, SIJ cartilage thickness, and total SIJ cartilage volume were identified. Based on these reconstructions, 281 finite element models were created to simulate SIJ mechanical loading. It was found that SIJ cartilage thickness only weakly depended on age or laterality, while being strongly sex sensitive. Auricular surface area and SIJ cartilage volume depended weakly and non-linearly on age, peaking around menopause in females, but without significant laterality effect. Larger SIJs, characterized by greater auricular area and cartilage volume, exhibited reduced stress and deformation under loading. These findings highlight the significant role of SIJ morphology in its biomechanical response, suggesting a potential link between morphological variations and the risk of SIJ dysfunction. Understanding this relationship could improve diagnosis and targeted treatment strategies for SIJ-related conditions.

• MeSH
• Finite Element Analysis MeSH
• Biomechanical Phenomena physiology   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Stress, Mechanical MeSH
• Adolescent MeSH
• Young Adult MeSH
• Tomography, X-Ray Computed * MeSH
• Sacroiliac Joint * anatomy & histology   physiology   diagnostic imaging   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. It has been suggested that neurodevelopmental factors contribute to the etiology of BD, but a specific neurodevelopmental phenotype (NDP) of the disorder has not been identified. Our objective was to define and characterize an NDP in BD and validate its associations with clinical outcomes, polygenic risk scores, and treatment responses. METHODS: We analyzed the FondaMental Advanced Centers of Expertise for Bipolar Disorders cohort of 4468 patients with BD, a validation cohort of 101 patients with BD, and 2 independent replication datasets of 274 and 89 patients with BD. Using factor analyses, we identified a set of criteria for defining NDP. Next, we developed a scoring system for NDP load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and gender with bootstrap replications. RESULTS: Our study established an NDP in BD consisting of 9 clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention-deficit/hyperactivity disorder, early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, and specific learning disorders. Patients with higher NDP load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between NDP load and polygenic risk score for attention-deficit/hyperactivity disorder, suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and attention-deficit/hyperactivity disorder. CONCLUSIONS: The proposed NDP constitutes a promising clinical tool for patient stratification in BD.

• MeSH
• Bipolar Disorder * genetics   MeSH
• Adult MeSH
• Phenotype * MeSH
• Attention Deficit Disorder with Hyperactivity genetics   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Multifactorial Inheritance genetics   MeSH
• Neurodevelopmental Disorders genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

This study aimed to investigate the effects of performing either eccentric-only (ECC) or eccentric-concentric (ECC-CON) back squats (BS) with a supramaximal load on countermovement jump (CMJ) performance. Changes in front thigh skin surface temperature and mechanical properties (oscillation frequency and stiffness) of the vastus lateralis were also examined. Fourteen male powerlifters participated in this study (age: 22.5 ± 2.3 years, body weight: 84.2 ± 11.1 kg, height: 178 ± 7 cm, training experience: 5.4 ± 1.6 years, BS one-repetition maximum [1RM]: 177 ± 22.8 kg). The experimental sessions included 2 sets of 2 BS at 110% 1RM of either ECC-CON (load distributed by half on the barbell [55%] and on weight releasers [55%]) or ECC (only eccentric phase of BS) and CTRL with no CA applied. CMJ performance, mechanical properties, and skin surface temperature were measured before and at the third, sixth, ninth, and 12th min. After each protocol, only the ECC-CON condition led to a significant increase in CMJ height after individual optimal rest time compared to pre-CA (38.1 ± 5.2 vs. 39.8 ± 5.0 cm; p = 0.003; effect size [ES] = 0.32; Δ = 4.9 ± 5.0%) with a significant rise in skin surface temperature (32.98 ± 1.24 vs. 33.69 ± 0.96°C; p = 0.006; ES = 0.62; Δ = 2.2 ± 2.6%) and no significant changes in mechanical properties of the vastus lateralis. The ECC-CON condition led to a significant acute improvement in CMJ height and an increase in front thigh skin surface temperature among powerlifters. The ECC-CON supramaximal lower limb PAPE protocol should be effectively used among males representing high levels of lower limb muscle strength (>2 × body mass).

• MeSH
• Biomechanical Phenomena MeSH
• Quadriceps Muscle physiology   MeSH
• Adult MeSH
• Muscle, Skeletal physiology   MeSH
• Humans MeSH
• Young Adult MeSH
• Resistance Training MeSH
• Athletic Performance * physiology   MeSH
• Thigh physiology   MeSH
• Muscle Strength physiology   MeSH
• Skin Temperature * physiology   MeSH
• Weight Lifting * physiology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Publication type
• Journal Article MeSH

Alzheimer's disease (AD) is the most common form of dementia. Characterized by progressive neurodegeneration, AD typically begins with mild cognitive decline escalating to severe impairment in communication and responsiveness. It primarily affects cerebral regions responsible for cognition, memory, and language processing, significantly impeding the functional independence of patients. With nearly 50 million dementia cases worldwide, a number expected to triple by 2050, the need for effective treatments is more urgent than ever. Recent insights into the association between obesity, type 2 diabetes mellitus, and neurodegenerative disorders have led to the development of promising treatments involving antidiabetic and anti-obesity agents. One such novel promising candidate for addressing AD pathology is a lipidized analogue of anorexigenic peptide called prolactin-releasing peptide (palm11-PrRP31). Interestingly, anorexigenic and orexigenic peptides have opposite effects on food intake regulation, however, both types exhibit neuroprotective properties. Recent studies have also identified ghrelin, an orexigenic peptide, as a potential neuroprotective agent. Hence, we employed both anorexigenic and orexigenic compounds to investigate the common mechanisms underpinning their neuroprotective effects in a triple transgenic mouse model of AD (3xTg-AD mouse model) combining amyloid-beta (Aβ) pathology and Tau pathology, two hallmarks of AD. We treated 3xTg-AD mice for 4 months with two stable lipidized anorexigenic peptide analogues - palm11-PrRP31, and liraglutide, a glucagon-like peptide 1 (GLP-1) analogue - as well as Dpr3-ghrelin, a stable analogue of the orexigenic peptide ghrelin, and using the method of immunohistochemistry and western blot demonstrate the effects of these compounds on the development of AD-like pathology in the brain. Palm11-PrRP31, Dpr3-ghrelin, and liraglutide reduced intraneuronal deposits of Aβ plaque load in the hippocampi and amygdalae of 3xTg-AD mice. Palm11-PrRP31 and Dpr3-ghrelin reduced microgliosis in the hippocampi, amygdalae, and cortices of 3xTg-AD mice. Palm11-PrRP31 and liraglutide reduced astrocytosis in the amygdalae of 3xTg-AD mice. We propose that these peptides are involved in reducing inflammation, a common mechanism underlying their therapeutic effects. This is the first study to demonstrate improvements in AD pathology following the administration of both orexigenic and anorexigenic compounds, highlighting the therapeutic potential of food intake-regulating peptides in neurodegenerative disorders.

• MeSH
• Alzheimer Disease * drug therapy   metabolism   pathology   MeSH
• Amyloid beta-Peptides metabolism   MeSH
• Amyloid beta-Protein Precursor genetics   metabolism   MeSH
• Ghrelin pharmacology   analogs & derivatives   therapeutic use   metabolism   MeSH
• Prolactin-Releasing Hormone * analogs & derivatives   pharmacology   MeSH
• Humans MeSH
• Liraglutide pharmacology   therapeutic use   MeSH
• Disease Models, Animal * MeSH
• Mice, Inbred C57BL MeSH
• Mice, Transgenic * MeSH
• Mice MeSH
• Neuroprotective Agents pharmacology   therapeutic use   MeSH
• Neuroinflammatory Diseases drug therapy   metabolism   MeSH
• Presenilin-1 genetics   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

The vertebrate visual cycle hinges on enzymatically converting all-trans-retinol (at-ROL) into 11-cis-retinal (11c-RAL), the chromophore that binds to opsins in photoreceptors, forming light-responsive pigments. When struck by a photon, these pigments activate the phototransduction pathway and initiate the process of vision. The enzymatic isomerization of at-ROL, crucial for restoring the visual pigments and preparing them to receive new light stimuli, relies on various enzymes found in both the photoreceptors and retinal pigment epithelium cells. To function effectively, retinoids must shuttle between these two cell types. Retinol-binding protein 3 (RBP3), located in the interphotoreceptor matrix, probably plays a pivotal role in this transport mechanism. Comprised of four retinoid-binding modules, RBP3 also binds fatty acids, potentially aiding retinal function by facilitating the loading and unloading of different retinoids at specific cell types thereby directing the cycle. In this study, we present a 3.67 Å cryoEM structure of porcine RBP3, along with molecular docking analysis and corroborative in-solution small-angle X-ray scattering data for titration of RBP3 with relevant ligands, that also give insights on RBP3 conformational adaptability.

• MeSH
• X-Ray Diffraction MeSH
• Cryoelectron Microscopy methods   MeSH
• Protein Conformation MeSH
• Scattering, Small Angle * MeSH
• Models, Molecular MeSH
• Eye Proteins MeSH
• Swine MeSH
• Retinol-Binding Proteins * chemistry   metabolism   MeSH
• Molecular Docking Simulation MeSH
• Protein Binding MeSH
• Vitamin A metabolism   chemistry   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH

An excessive increase in reactive oxygen species (ROS) levels is one of the main causes of mitochondrial dysfunction. However, when ROS levels are maintained in balance with antioxidant mechanisms, ROS fulfill the role of signaling molecules and modulate various physiological processes. Recent advances in mitochondrial bioenergetics research have revealed a significant interplay between mitochondrial peroxiredoxins (PRDXs) and monoamine oxidase-A (MAO-A) in regulating ROS levels. Both proteins are associated with hydrogen peroxide (H2O2), MAO-A as a producer and PRDXs as the primary antioxidant scavengers of H2O2. This review focuses on the currently available knowledge on the function of these proteins and their interaction, highlighting their importance in regulating oxidative damage, apoptosis, and metabolic adaptation in the heart. PRDXs not only scavenge excess H2O2, but also act as regulatory proteins, play an active role in redox signaling, and maintain mitochondrial membrane integrity. Overexpression of MAO-A is associated with increased oxidative damage, leading to mitochondrial dysfunction and subsequent progression of cardiovascular diseases (CVD), including ischemia/reperfusion injury and heart failure. Considering the central role of oxidative damage in the pathogenesis of many CVD, targeting PRDXs activation and MAO-A inhibition may offer new therapeutic strategies aimed at improving cardiac function under conditions of pathological load related to oxidative damage. Keywords: Mitochondria, Peroxiredoxin, Monoamine oxidase-A, Reactive oxygen species, Cardioprotective signaling.

• MeSH
• Humans MeSH
• Monoamine Oxidase * metabolism   MeSH
• Oxidative Stress MeSH
• Peroxiredoxins * metabolism   MeSH
• Reactive Oxygen Species * metabolism   MeSH
• Signal Transduction * MeSH
• Mitochondria, Heart metabolism   enzymology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Arterial compliance (AC) is an important cardiovascular parameter characterizing mechanical properties of arteries. AC is significantly influenced by arterial wall structure and vasomotion, and it markedly influences cardiac load. A new method, based on a two-element Windkessel model, has been recently proposed for estimating AC as the ratio of the time constant T of the diastolic blood pressure decay and peripheral vascular resistance derived from clinically available stroke volume measurements and selected peripheral blood pressure parameters which are less prone to peripheral distortions. The aim of this study was to validate AC estimation using a virtual population generated by in silico model of the systemic arterial tree. In the second part of study, we analysed causal coupling between AC oscillations and variability of its potential determinants - systolic blood pressure and heart rate in healthy young human subjects. The pool of virtual subjects (n=3818) represented an extensive AC distribution. AC was estimated from the peripheral blood pressure curve and by the standard method from the aortic blood pressure curve. The proposed method slightly overestimated AC set in the model but both ACs were strongly correlated (r=0.94, p<0.001). In real data, we observed that AC dynamics was coupled with basic cardiovascular parameters variability independently of the autonomic nervous system state. In silico analysis suggests that AC can be reliably estimated by noninvasive method. The analysis of short-term AC variability together with its determinants could improve our understanding of factors involved in AC dynamics potentially improving assessment of AC changes associated with atherosclerosis process. Key words Arterial compliance, Cardiovascular model, Arterial blood pressure, Causal analysis, Volume-clamp photoplethysmography.

• MeSH
• Arteries * physiology   MeSH
• Vascular Resistance physiology   MeSH
• Adult MeSH
• Blood Pressure * physiology   MeSH
• Humans MeSH
• Young Adult MeSH
• Models, Cardiovascular * MeSH
• Computer Simulation * MeSH
• Compliance MeSH
• Heart Rate physiology   MeSH
• Vascular Stiffness physiology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Validation Study MeSH

Free radical polymerization technique was used to formulate Poloxamer-188 based hydrogels for controlled delivery. A total of seven formulations were formulated with varying concentrations of polymer, monomer ad cross linker. In order to assess the structural properties of the formulated hydrogels, Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM), and X-ray diffraction (XRD) were carried out. To assess the effect of pH on the release of the drug from the polymeric system, drug release studies were carried in pH 1.2 and 7.4 and it was found that release of the drug was significant in pH 7.4 as compared to that of pH 1.2 which confirmed the pH responsiveness of the system. Different kinetic models were also applied to the drug release to evaluate the mechanism of the drug release from the system. To determine the safety and biocompatibility of the system, toxicity study was also carried out for which healthy rabbits were selected and formulated hydrogels were orally administered to the rabbits. The results obtained suggested that the formulated poloxamer-188 hydrogels are biocompatible with biological system and have the potential to serve as controlled drug delivery vehicles.

• MeSH
• Acrylic Resins * chemistry   MeSH
• Calorimetry, Differential Scanning MeSH
• X-Ray Diffraction MeSH
• Hydrogels * chemistry   MeSH
• Hydrogen-Ion Concentration MeSH
• Rabbits MeSH
• Drug Delivery Systems MeSH
• Delayed-Action Preparations chemistry   pharmacokinetics   MeSH
• Microscopy, Electron, Scanning MeSH
• Drug Carriers chemistry   MeSH
• Poloxamer * chemistry   MeSH
• Spectroscopy, Fourier Transform Infrared MeSH
• Thermogravimetry MeSH
• Timolol * administration & dosage   pharmacokinetics   chemistry   MeSH
• Drug Liberation MeSH
• Animals MeSH
• Check Tag
• Rabbits MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

While the immunomodulation effects of per- and polyfluoroalkyl substances (PFASs) are described on the level of clinical signs in epidemiological studies (e.g., suppressed antibody response after vaccination), the underlying mechanism has still not been fully elucidated. To reveal mechanisms of PFAS exposure on immunity, we investigated the genome-wide transcriptomic changes of peripheral blood mononuclear cells (PBMCs) responding to PFAS exposure (specifically, exposure to PFPA, PFOA, PFNA, PFDA, PFUnDA, PFHxS, and PFOS). Blood samples and the chemical load in the blood were analyzed under the cross-sectional CELSPAC: Young Adults study. The overall aim of the study was to identify sensitive gene sets and cellular pathways conserved for multiple PFAS chemicals. Transcriptome networks related to adaptive immunity were perturbed by multiple PFAS exposure (i.e., blood levels of at least four PFASs). Specifically, processes tightly connected with late B cell development, such as B cell receptor signaling, germinal center reactions, and plasma cell development, were shown to be affected. Our comprehensive transcriptome analysis identified the disruption of B cell development, specifically the impact on the maturation of antibody-secreting cells, as a potential mechanism underlying PFAS immunotoxicity.

• MeSH
• Fluorocarbons * toxicity   MeSH
• Alkanesulfonic Acids * MeSH
• Environmental Pollutants * MeSH
• Leukocytes, Mononuclear MeSH
• Humans MeSH
• Young Adult MeSH
• Cross-Sectional Studies MeSH
• Transcriptome MeSH
• Check Tag
• Humans MeSH
• Young Adult MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

OBJECTIVES: Comparisons of material hardness may be affected by the indentation size effect (ISE), which is characterized by increasing hardness values at decreasing loads. This study aimed to assess the influence of load, dwell time and measurement method on ISE in dental resin-based composites with different filler content. METHODS: Knoop (HK) and Vickers (HV) microindentation hardness of Filtek Ultimate Universal Restorative (FU) and Filtek Supreme Flowable Restorative (FF) was measured under different loads (0.098-2.96 N, i.e. 10-300 gf) and dwell times (5-30 s). Their effects on HK and HV were evaluated using repeated measures ANOVA, which was also used to compare the measurement methods. Coefficients of Meyer's equation, proportional specimen resistance (PSR) model and a modified PSR model were calculated using regression analyses. RESULTS: ISE was more pronounced for the highly-filled FU than for the less-filled FF, and HK was more susceptible to ISE than HV. The effect of dwell time was similar for both materials and measurement methods; hardness values decreased with dwell time, significantly between 5 s and 30 s. SIGNIFICANCE: The possible presence of ISE should be considered when determining measurement conditions for the microindentation hardness of dental resin-based composites. HV was found to be less sensitive to ISE and provided stable hardness values at lower loads than HK. Due to the high variability of composites, any hardness measurement should be preceded by mapping the effect of load to ensure that load-independent hardness is measured. If hardness values continue to decrease in the whole range of increasing loads, load-independent hardness can be calculated using the PSR model.

• MeSH
• Composite Resins * chemistry   MeSH
• Materials Testing * MeSH
• Hardness Tests MeSH
• Hardness * MeSH
• Publication type
• Journal Article MeSH