Functional Changes Research Articles

Right Ventricle and Autoimmune Diseases.

Autoimmune diseases can express pathologies in specific organs (e.g. thyroid, pancreas, skin) or generate systemic pathologies (generalized lupus erythematosus, rheumatoid arthritis, systemic sclerosis), the latter usually present systemic inflammatory phenomena. Some studies have reported alterations in right ventricular contractility in patients with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and juvenile idiopathic arthritis, which may contribute to the known outcome of increased cardiovascular risk. However, there is not much information available on the causes that generate these alterations, the most likely being small vessel damage and fibrosis due to subclinical inflammation.1-5 In this sense, the disease in which the alterations of the right ventricle have been more studied is systemic sclerosis, specifically at the changes induced due to pulmonary arterial hypertension, this being one of the main causes of death in this group of patients after the significant decrease in mortality associated with the sclerodermic renal crisis with the treatment of angiotensin-converting enzyme inhibitors. In this review, we will focus on explaining the structural and functional changes that occur in the right ventricle of patients with systemic sclerosis, from early alterations to late complications. In this context, it is necessary to distinguish between right heart alterations that occur in patients with systemic sclerosis and pulmonary arterial hypertension and those that occur without pulmonary arterial hypertension and that can be attributed to other causes such as microvascular damage or myocardial fibrosis.

The influence of nanoparticle size, concentration, and functionalization on drilling fluid filtration properties

This research investigates the effect of the surface properties of silicon dioxide (SiO2) nanoparticles on the filtration properties of water-based drilling fluid. The nanoparticles were synthesized in-house using a one-step sol-gel method and functionalized into different charges. Different sizes, concentrations, and functionalization of water-based drilling fluid were subjected to standard API and HPHT filtration tests. Regression analysis and ANOVA were carried out to develop a model for future prediction and classify each independent variable's significance. The result shows that the positively charged nanoparticles had better filtration properties, as evidenced by the lower filtrate volume. Functionalization levels had minimal impact on filtration properties, and the effect of concentration was insignificant above 0.4 v/v%. In terms of nanoparticle size, 120 nm showed a more consistent result despite varying concentration and functionalization. In contrast, smaller nanoparticle sizes are more susceptible to changes in concentration and functionalization but could produce the least filtrate volume with the appropriate combination of concentration and functionalization. Filtrate analysis shows that about 25–28 % of the drilling fluid nanoparticles can infiltrate the porous media. Furthermore, this study challenges existing models on the improvement of the filtration properties by using nanoparticles. While previous hypothesis relied on physical bridging mechanism, new evidence from this research suggests that the enhancement is primarily based on the surface properties of the nanoparticles. Specifically, the nanoparticles envelop the barite through monolayer adsorption, reducing the angularity and increasing the reaction sites with water molecules. This inhibits the mobility of the water molecules across the filter cakes, providing a novel understanding of the mechanisms underlying nanoparticle-enhanced filtration properties of drilling fluids. In summary, the filtration properties of water-based drilling fluid with nanoparticles are significantly influenced by the surface properties of the nanoparticles, with positively charged nanoparticles demonstrating superior performance in stable conditions.

Structural and functional abnormalities in the medial prefrontal cortex were associated with pain and depressive symptoms in patients with adhesive capsulitis.

Chronic pain and depression have been shown to coexist in patients with adhesive capsulitis (AC). Recent studies identified the shared brain plasticity between pain and depression; however, how such neuroplasticity contributes to AC remains unclear. Here, we employed a combination of psychophysics, structural MRI, and functional MRI techniques to examine the brain's structural and functional changes in AC. Fifty-two patients with AC and 52 healthy controls (HCs) were included in our study. Voxelwise comparisons were performed to reveal the differences in grey matter volume (GMV) and regional homogeneity (ReHo) between AC and HCs. Furthermore, region of interest to whole brain functional connectivity (FC) was calculated and compared between the groups. Finally, Pearson correlation coefficients were computed to reveal the association between clinical data and brain alterations. Mediation analyses were performed to investigate the path association among brain alterations and clinical measures. Three main findings were observed: (1) patients with AC exhibited a higher depression subscale of hospital anxiety and depression scale (HADS-D) score correlating with the GMV within the right medial prefrontal cortices (mPFC) compared with HCs; (2) relative to HCs, patients with AC exhibited lower ReHo within the right mPFC, which largely overlapped with the structural abnormalities; (3) the impact of pain duration on HADS-D score was mediated by ventral part of medial prefrontal cortices (vmPFC) GMV in patients with AC. In summary, our current findings suggest that vmPFC alterations correlate with both the pain duration and the emotional comorbidities experienced by patients with AC. Our research provides an enhanced comprehension of the underlying mechanisms of AC, thereby facilitating the development of more effective treatment approaches for AC.

Abstract 5567: Breast cancer cell alteration of immune cell transcriptome through indirect communication

Abstract Crosstalk between tumor and non-tumor cells plays an important role in cancer progression and metastasis often leading to a modification of non-malignant cells into pro-oncogenic phenotypes. Understanding this process is important for diagnostic and therapeutic advances. We previously reported clinical validation results for a new way to detect early-stage breast cancer using a panel of RNA biomarkers from whole blood and a machine learning software-powered testing system. Recently, we showed that immune cells undergo transcriptomic and functional changes upon direct contact with breast cancer cells. Here, we report results from investigation of indirect communication between breast cancer and immune cells leading to cancer-driven immune cell transformation and activation of multiple oncogenic pathways. To characterize these modifications, we performed RNAseq and pathway analysis on a human monocytic cell line, THP1, exposed to media from triple negative breast cancer (TNBC) cells (MDA-MB-231) in culture. Our results demonstrate that 24 hours of THP1 cell exposure to soluble factors secreted by tumor cells leads to significant gene modulation, with over 1,100 differentially expressed genes (|Fold Change|>2; p<0.05). KEGG and Reactome enrichment analysis revealed overlap of multiple pathways between THP1 cells exposed to direct and indirect cancer cell contact conditions, such as cytokine-cytokine receptor interaction, JAK-STAT signaling pathways and others. TNF, NMP1, STING1 and TGM2 were identified as key upstream regulators potentially driving this transformation in both direct and indirect contact conditions. The S100 pathway, which we previously found to be activated by fluid shear stress in MDA-MB-231 cells was also activated in THP1 cells upon both direct and indirect contact. The observed gene expression changes in THP1 cells exposed to media from MDA-MB-231 suggests that indirect intercellular communication alone can transmit an oncogenic signal. These results support a role for secreted factors from breast cancer cells in transforming immune cells and modulating the gene expression markers detected by our blood test, expanding the potential for leveraging this type of tumor education response in advancing cancer detection and treatment. Citation Format: Jacob Kennard, Karen Norek, Kenneth Fuh, Robert D. Shepherd, Kristina D. Rinker, Olesya A. Kharenko. Breast cancer cell alteration of immune cell transcriptome through indirect communication [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5567.

Abstract 1258: A cholesterol metabolite can modulate neutrophil-derived extracellular vesicles to promote breast cancer cell epithelial to mesenchymal transition (EMT) and stemness

Abstract Breast cancer is the second leading cause of cancer-related death in women, with mortality most often due to metastatic recurrence. Elevated cholesterol is associated with poor prognosis, with several potential mechanisms proposed. Work in murine models found that many of the pro-metastatic actions of cholesterol required the enzymatic conversion of cholesterol to 27-hydroxycholesterol (27HC), which functions as a ligand for both the estrogen receptors (ERs) and liver X receptors (LXRs). Importantly, we have found that 27HC promotes metastasis, in part through its actions on neutrophils. When examining mechanisms, we have made the observation that 27HC resulted in increased secretion of small extracellular vesicles (sEVs) from neutrophils. These 27HC-neutrophil-sEVs independently promote metastatic colonization. Since we have found that breast cancer cell lines can take up neutrophil-derived sEVs, we hypothesized that 27HC results in altered cargo within sEVs which leads to functional changes within cancer cells, the ultimate consequence of which being their increased metastatic potential. Using a non-biased small RNA-seq approach we have found that sEVs from 27HC-treated neutrophils had an altered miRNA signature. Bioinformatic analysis revealed several downregulated miRNAs from the let-7 subgroup. Let-7 miRs are known to target several genes associated with the WNT/β-catenin pathway, a pathway strongly implicated in epithelial to mesenchymal transition (EMT) and cancer cell stemness. Strikingly, breast cancer cells treated with sEVs from neutrophils treated with 27HC lost their adherent properties and adopted a mesenchymal and stem-like phenotype. In order to elucidate the mechanism by which these sEVs promote EMT and stemness, we performed comprehensive transcriptomics through time. Weighted gene co-expression network analysis (WGCNA) confirmed these phenotypic shifts, and implicated the WNT/β-catenin pathway, providing support to our hypothesis that the loss of let-7 miRs is the upstream mediator. Collectively, our data suggests that 27HC increases metastasis in part through its effects on neutrophils, by shifting sEVs cargo towards a loss of protective microRNA, resulting in increased EMT and stemness, and thus the ability of cancer cells to migrate, invade and metastasize. Funding: National Cancer Institute (ERN: R01CA234025) Department of Defense (ERN: BCRP Era of Hope Award), and Beckman Institute for Advanced Science and Technology (NK) Citation Format: Natalia J. Krawczynska, Yu Wang, Anasuya Das Gupta, Jenny Drnevich, Julie Ostrander, Erik R. Nelson. A cholesterol metabolite can modulate neutrophil-derived extracellular vesicles to promote breast cancer cell epithelial to mesenchymal transition (EMT) and stemness [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1258.

DEVELOPMENT OF ULTRASTRUCTURAL CHANGES IN DIAPHRAGM MUSCLE FIBERS DURING PARTIAL TRACHEAL STENOSIS IN YOUNG SEXUALLY IMMATURE RATS

Introduction. The study of congenital pathology of the respiratory tract in children is of great importance for theoretical and clinical pediatric otolaryngology. Currently, in the scientific literature there are single works concerning the study of the pathogenesis and clinic of laryngomalacia. First of all, this concerns the effect of acute and chronic hypoxia on the muscles of the respiratory system, in particular, the diaphragm. The aim of thіs work is to reveal the effect of hypoxia on the development of pronounced structural and functional changes in the diaphragm muscles of sexually immature animals when modeling partial tracheal occlusion. Materials and methods. Surgical partial occlusion of the trachea was performed on in sexually immature Wistar rats; we applied electron microscopy, morphometric and statistical research methods.
 Results. The obtained data demonstrated that the muscle fibers of the diaphragm are characterized by significant structural, functional and metabolic resistance to the development of acute or chronic hypoxia due to limited lung ventilation in rats. The density of muscle fibers did not change in any of the used terms of the experiment (7 and 21 days). On the 7th day of hypoxic exposure, a change in the state of the matrix of mitochondria of muscle fibers was observed, which was accompanied by partial ultrastructural rearrangements of the organization of these organelles. At the same time, no significant changes were observed during histological studies. Electrongrams demonstrated the ultrastructural damages were mainly limited to focal reduction of myofibrils and an increase in the mitochondria's diameter and found as especially pronounced on day 21 (a state of chronic hypoxia) on the muscular component of the respiratory system in rats. These changes are accompanied by the development of dystrophic disorders in the diaphragm myofibrils. On day 21 changes in the transendothelial transport of substance molecules were also detected. This was based on establishing the fact of a significant reduction in the number of pinocytosis vesicles in the cytoplasm of endothelial cells of diaphragm hemocapillaries in animals with partial tracheal occlusion. Disruption of the structural organization of actomyosin complexes was revealed in muscle fibers due to pathological changes in the mitochondria of myofibrils. It should be noted the development of destruction or complete loss of an important ultrastructural component of muscle fibers, Z-lines. These changes were completely absent on the 7th day following the influence of partial tracheal occlusion and the development of acute hypoxia. Moreover, on day 21, partial lysis of a significant amount of myofilaments of muscle fibers was observed. In addition, the development of the process of fiber swelling was detected against the background of which the above-mentioned ultrastructural destruction of the muscular component in the diaphragm was observed. These changes indicate the need for earlier treatment of laryngomalacia in children. The delay in surgical intervention leads to the development of severe or irreversible structural changes not only in the respiratory organs, but also in their muscular system.
 Conclusion. The muscular elements of the diaphragm have the pronounced and significant resistance to the state of hypoxia under conditions of limited ventilation of the respiratory tract. Ultrastructural and morphometric data, found on the 21st day after the modeling of partial tracheal stenosis, are not only of a compensatory and adaptive in nature, but also signs of pronounced disorders in the muscle fibers of the central part of the diaphragm in test animals.

A Retrospective Analysis of Temporal Lobe Gliosis after Middle Fossa Resection of Small Vestibular Schwannomas.

The middle cranial fossa (MCF) approach is a well-established procedure in surgery of the internal auditory canal, as well as with the retrosigmoid and translabyrinthine approaches. It is commonly used in the hearing-preserving microsurgery of small vestibular schwannomas (VS). The debate about the "best" approach for the microsurgery of small VS without contact to the brainstem is controversial. It has been stated that the MCF approach leads to irreversible damage to the temporal lobe, which may be evident in follow-up magnet resonance imaging (MRI) as gliosis in up to 70% of patients. This study represents a retrospective chart analysis conducted at a tertiary university hospital. Here, 76 postoperative MRIs were re-evaluated by an experienced neuroradiologist and compared with the preoperative images. Temporal lobe gliosis was classified on an ordinal scale as absent, slight, moderate or severe. Occurrence of gliosis was matched to the clinical predictors (tumor stage, tumor volume, sex, age, and side). No case of severe or moderate gliosis was found in the patient group. Slight gliosis of the temporal lobe was rare and was only detected in four patients (5%). There was no relation between clinical predictors and the incidence of gliosis. In our cohort, postoperative MR imaging did not reveal relevant damage to the temporal lobe parenchyma. This confirms the safe concept of microsurgery of small tumors via the middle fossa approach. The severe glioses described in other studies may be caused by a forced insertion of the retractor or by more extended approaches. However, further prospective neurocognitive studies seem to be necessary in order to assess functional changes in the temporal lobe.

Using virtual reality-based physical activity to change the mental health and cognitive function of karate athletes

Purpose. The use of virtual reality technology in the field of sports is increasing, but there is a lack of evidence reporting the effects of virtual reality to change the level of mental health and cognitive function in Karate athletes through mixed research methods. This study to determine how virtual reality-based physical activity affected athletes' levels of mental health and cognitive function.
 Material and methods. This study involved male Karate athletes from Cendikia Leadership School in Indonesia (n=30). The athletes were allocated to the experimental group (n=15) and control group (n=15).
 Results. First finding of the quantitative study showed that before the experiment there was no difference in the scores of mental health and cognitive function in the two groups. The second finding showed that there was a difference after the experiment.  In qualitative study, athletes revealed their perception that the advantages of virtual reality-based physical activity were fun, easy to implement, and can be carried out without the supervision of a coach. Moreover, they also mentioned the weakness of this tool, namely not all athletes have virtual reality tools, the impact to their eye health, exercise must be carried out in a safe place.
 Conclusions. Thus, this study concluded that physical activity based on virtual reality was proven to be effective in changing of mental health and cognitive function of Karate athletes.

Mutation of SOCS2 induces structural and functional changes in mammary development.

Lactation is an essential process for mammals. In sheep, the R96C mutation in suppressor of cytokine signaling 2 (SOCS2) protein is associated with greater milk production and increased mastitis sensitivity. To shed light on the involvement of R96C mutation in mammary gland development and lactation, we developed a mouse model carrying this mutation (SOCS2KI/KI). Mammary glands from virgin adult SOCS2KI/KI mice presented a branching defect and less epithelial tissue, which were not compensated for in later stages of mammary development. Mammary epithelial cell (MEC) subpopulations were modified, with mutated mice having three times as many basal cells, accompanied by a decrease in luminal cells. The SOCS2KI/KI mammary gland remained functional; however, MECs contained more lipid droplets versus fat globules, and milk lipid composition was modified. Moreover, the gene expression dynamic from virgin to pregnancy state resulted in the identification of about 3000 differentially expressed genes specific to SOCS2KI/KI or control mice. Our results show that SOCS2 is important for mammary gland development and milk production. In the long term, this finding raises the possibility of ensuring adequate milk production without compromising animal health and welfare.

Impact effects of COVID-19 pandemic on chronic disease patients: A longitudinal prospective study.

To assess the effects of COVID-19 pandemic on clinical variables as part of the routine clinical monitoring of patients with chronic diseases in primary care. A prospective longitudinal study was conducted in primary care centres of the Andalusian Health Service. Data were recorded before the pandemic (T1), during the declaration of the state of emergency (T2) and in the transition phase (T3). The Barthel index and the Short Portable Mental Status Questionnaire (SPMSQ) were used to analyse functional and cognitive changes at the three time points. HbA1c, systolic and diastolic blood pressure, heart rate, BMI and lipid levels were assessed as clinical variables. Descriptive statistics and non-parametric chi-square test were used for analysis. STROBE checklist was used for the preparation of this paper. A total fo148 patients with chronic conditions were included in the analysis. Data analysis revealed in T2 only significant reductions in BMI, total levels of cholesterol and HDL during the onset of the pandemic. Barthel Index, SPMSQ, blood pressure and triglycerides and LDL levels worsened in T2, and the negative effects were maintained in T3. Compared to pre-pandemic values, HbA1c levels improved in T3, but HDL levels worsened. COVID-19 has drastically disrupted several functional, cognitive and biological variables. These results may be useful in identifying clinical parameters that deserve closer attention in the case of a new health crisis. Further studies are needed to assess the potential impacts of each specific chronic condition. Cognitive and functional status, blood pressure and triglycerides and LDL levels worsen in short term, maintaining the negative effects in medium-term.

Chronic Pain-Related Cognitive Deficits: Preclinical Insights into Molecular, Cellular, and Circuit Mechanisms.

Cognitive impairment is a common comorbidity of chronic pain, significantly disrupting patients' quality of life. Despite this comorbidity being clinically recognized, the underlying neuropathological mechanisms remain unclear. Recent preclinical studies have focused on the fundamental mechanisms underlying the coexistence of chronic pain and cognitive decline. Pain chronification is accompanied by structural and functional changes in the neural substrate of cognition. Based on the developments in electrophysiology and optogenetics/chemogenetics, we summarized the relevant neural circuits involved in pain-induced cognitive impairment, as well as changes in connectivity and function in brain regions. We then present the cellular and molecular alternations related to pain-induced cognitive impairment in preclinical studies, mainly including modifications in neuronal excitability and structure, synaptic plasticity, glial cells and cytokines, neurotransmitters and other neurochemicals, and the gut-brain axis. Finally, we also discussed the potential treatment strategies and future research directions.

Distinct neural signatures of pulvinar in C9orf72 amyotrophic lateral sclerosis mutation carriers and noncarriers.

Thalamic alterations have been reported as a major feature in presymptomatic and symptomatic patients carrying the C9orf72 mutation across the frontotemporal dementia-amyotrophic lateral sclerosis (ALS) spectrum. Specifically, the pulvinar, a high-order thalamic nucleus and timekeeper for large-scale cortical networks, has been hypothesized to be involved in C9orf72-related neurodegenerative diseases. We investigated whether pulvinar volume can be useful for differential diagnosis in ALS C9orf72 mutation carriers and noncarriers and how underlying functional connectivity changes affect this region. We studied 19 ALS C9orf72 mutation carriers (ALSC9+) accurately matched with wild-type ALS (ALSC9-) and ALS mimic (ALSmimic) patients using structural and resting-state functional magnetic resonance imaging data. Pulvinar volume was computed using automatic segmentation. Seed-to-voxel functional connectivity analyses were performed using seeds from a pulvinar functional parcellation. Pulvinar structural integrity had high discriminative values for ALSC9+ patients compared to ALSmimic (area under the curve [AUC] = 0.86) and ALSC9- (AUC = 0.77) patients, yielding a volume cutpoint of approximately 0.23%. Compared to ALSmimic, ALSC9- showed increased anterior, inferior, and lateral pulvinar connections with bilateral occipital-temporal-parietal regions, whereas ALSC9+ showed no differences. ALSC9+ patients when compared to ALSC9- patients showed reduced pulvinar-occipital connectivity for anterior and inferior pulvinar seeds. Pulvinar volume could be a differential biomarker closely related to the C9orf72 mutation. A pulvinar-cortical circuit dysfunction might play a critical role in disease progression and development, in both the genetic phenotype and ALS wild-type patients.

Sex Differences in the Role of Multimorbidity on Poststroke Disability: The Taiwan Stroke Registry.

Multimorbidity is common in patients who experience stroke. Less is known about the effect of specific multimorbidity patterns on long-term disability in patients with stroke. Furthermore, given the increased poststroke disability frequently seen in female vs male patients, it is unknown whether multimorbidity has a similar association with disability in both sexes. We assessed whether specific multimorbidity clusters were associated with greater long-term poststroke disability burden overall and by sex. In the Taiwan Stroke Registry, an ongoing nationwide prospective registry, patients with first-ever ischemic stroke were enrolled; this analysis is restricted to those individuals surviving to at least 6 months poststroke. Using a hierarchical clustering approach, clusters of prestroke multimorbidity were generated based on 16 risk factors; the algorithm identified 5 distinct clusters. The association between clusters and 12-month poststroke disability, defined using the modified Rankin Scale (mRS), was determined using logistic regression models, with additional models stratified by sex. The longitudinal association between multimorbidity and functional status change was assessed using mixed-effects models. Nine-thousand eight hundred eighteen patients with first-ever ischemic stroke were included. The cluster with no risk factors was the reference, "healthier" risk group (N = 1,373). Patients with a cluster profile of diabetes, peripheral artery disease (PAD), and chronic kidney disease (CKD) (N = 1882) had significantly greater disability (mRS ≥ 3) at 1 month (OR [95% CI] = 1.36 [1.13-1.63]), 3 months (OR [95% CI] = 1.27 [1.04-1.55]), and 6 months (OR [95% CI] = 1.30 [1.06-1.59]) but not at 12 months (OR [95% CI] = 1.16 [0.95-1.42]) than patients with a healthier risk factor profile. In the sex-stratified analysis, the associations with this risk cluster remained consistent in male patients (OR [95% CI] = 1.42 [1.06-1.89]) at 12 months, who also had a higher comorbidity burden, but not in female patients (OR [95% CI] = 0.95 [0.71-1.26]), who had higher proportions of severe strokes and severe disability (p-interaction = 0.04). Taiwanese patients with multimorbidity, specifically the concurrent presence of diabetes, PAD, and CKD, had higher odds of a worse functional outcome in the first 6 months poststroke. Clusters of multimorbidity may be less informative for long-term disability in female patients. Further studies should evaluate other mechanisms for worse disability in female patients poststroke.

Breathing changes following mini-implant-supported maxillary skeletal expander treatment in late adolescent or adult patients : Assessment of objective and subjective functional breathing changes.

The aim of this study was to assess objective and subjective breathing changes in adult patients who underwent maxillary skeletal expansion with the mini-implant-supported maxillary skeletal expander (MSE). Twenty-nine patients (mean age 18.1 ± 4.3years) who underwent expansion using the MSE were compared pre- and posttreatment and with acontrol group (mean age 19.9 ± 2.6years) to assess objective and subjective functional breathing changes. Objective measurements of the airway including peak nasal inspiratory flow (PNIF) and peak oral inspiratory flow (POIF) were measured utilizing the In-Check medical device (Clement Clarke, Harlow, United Kingdom). Patients reported subjective breathing assessment utilizing the visual analog scale (VAS). Intragroup comparisons were performed with Wilcoxon tests and intergroup comparison with Mann-WhitneyU tests. Spearman correlation coefficients were calculated among the studied variables (P < 0.05). Following MSE treatment, there were significantly higher values for PNIF total (P < 0.0001), PNIF right (P < 0.0001), PNIF left (P < 0.0001), and POIF (P < 0.01) compared to pretreatment and control group results. Also, patients reported asignificant decrease in troubled breathing as measured by the VAS for breathing through the right nostril (P < 0.01), left nostril (P < 0.001), and both nostrils (P < 0.01). Comparing the objective and subjective variables for both the pre-MSE or post-MSE groups, the results indicated no significant correlation between total PNIF and total VAS. However, the values had significant correlations between PNIF and VAS on each side when the patients were asked to block one nostril. Objective functional breathing measurements were increased immediately after treatment with MSE. Subjective functional breathing measurements changes were significantly higher after MSE treatment and compared with the control group. MSE presents anonsurgical alternative to achieving orthopedic expansion in adult patients which may provide abenefit for patients with nasal airway obstruction.

Late-adolescent onset of prefrontal endocannabinoid control of hippocampal and amygdalar inputs and its impact on trace-fear conditioning behavior.

Prefrontal cortex (PFC) maturation during adolescence is characterized by structural and functional changes, which involve the remodeling of GABA and glutamatergic synapses, as well as changes in the endocannabinoid system. Yet, the way PFC endocannabinoid signaling interacts with local GABA and glutamatergic function to impact its processing of afferent transmission during the adolescent transition to adulthood remains unknown. Here we combined PFC local field potential recordings with local manipulations of 2-AG and anandamide levels to assess how PFC endocannabinoid signaling is recruited to modulate ventral hippocampal and basolateral amygdalar inputs in vivo in adolescent and adult male rats. We found that the PFC endocannabinoid signaling does not fully emerge until late-adolescence/young adulthood. Once present, both 2-AG and anandamide can be recruited in the PFC to limit the impact of hippocampal drive through a CB1R-mediated mechanism whereas basolateral amygdalar inputs are only inhibited by 2-AG. Similarly, the behavioral effects of increasing 2-AG and anandamide in the PFC do not emerge until late-adolescence/young adulthood. Using a trace fear conditioning paradigm, we found that elevating PFC 2-AG levels preferentially reduced freezing behavior during acquisition without affecting its extinction. In contrast, increasing anandamide levels in the PFC selectively disrupted the extinction of trace fear memory without affecting its acquisition. Collectively, these results indicate a protracted recruitment of PFC endocannabinoid signaling, which becomes online in late adolescence/young adulthood as revealed by its impact on hippocampal and amygdalar-evoked local field potential responses and trace fear memory behavior.

Right Ventricular Structure and Function in Adolescent Athletes: A 3D Echocardiographic Study.

The aim of this study was to characterize the right ventricular (RV) contraction pattern and its associations with exercise capacity in a large cohort of adolescent athletes using resting three-dimensional echocardiography (3DE). We enrolled 215 adolescent athletes (16±1 years, 169 males, 12±6 hours of training/week) and compared them to 38 age and sex-matched healthy, sedentary adolescents. We measured the 3DE-derived biventricular ejection fractions (EF). We also determined the relative contributions of longitudinal EF (LEF/RVEF) and radial EF (REF/RVEF) to the RVEF. Same-day cardiopulmonary exercise testing was performed to calculate VO2/kg. Both LV and RVEFs were significantly lower (athletes vs. controls; LVEF: 57±4 vs 61±3, RVEF: 55±5 vs 60±5%, p<0.001). Interestingly, while the relative contribution of radial shortening to the global RV EF was also reduced (REF/RVEF: 0.40±0.10 vs 0.49±0.06, p<0.001), the contribution of the longitudinal contraction was significantly higher in athletes (LEF/RVEF: 0.45±0.08 vs 0.40±0.07, p<0.01). The supernormal longitudinal shortening correlated weakly with a higher VO2/kg (r=0.138, P=0.044). Similarly to the adult athlete's heart, the cardiac adaptation of adolescent athletes comprises higher biventricular volumes and lower resting functional measures with supernormal RV longitudinal shortening. Characteristic exercise-induced structural and functional cardiac changes are already present in adolescence.

Mechanisms underlying morphological and functional changes of cilia in fibroblasts derived from patients bearing ARL3T31A and ARL3T31A/C118F mutations.

ARL3 is essential for cilia development, and mutations in ARL3 are closely associated with ciliopathies. In a previous study, we observed distinct phenotypes of retinal dystrophy in patients with heterozygous ARL3T31A and compound heterozygous ARL3T31A/C118F mutations, indicating that different mutation types may exert diverse effects on their functions. Here, we generated transformed immortal fibroblast cells from patients carrying heterozygous ARL3T31A and compound heterozygous ARL3T31A/C118F mutations, and systematically evaluated their cilia morphology and function, which were further validated in ARPE-19 cells. Results showed that both ARL3T31A and ARL3T31A/C118F mutations led to a decrease in cilium formation. The ARL3T31A/C118F mutations caused significantly elongated cilia and impaired retrograde transport, whereas the ARL3T31A mutation did not induce significant changes in fibroblasts. RNA-sequencing results indicated that compared to ARL3T31A , ARL3T31A/C118F fibroblasts exhibited a higher enrichment of biological processes related to neuron projection development, tissue morphogenesis, and extracellular matrix (ECM) organization, with noticeable alterations in pathways such as ECM-receptor interaction, focal adhesion, and TGF-β signaling. Similar changes were observed in the proteomic results in ARPE-19 cells. Core regulated genes including IQUB, UNC13D, RAB3IP, and GRIP1 were specifically downregulated in the ARL3T31A/C118F group, and expressions of IQUB, NPM2, and SLC38A4 were further validated. Additionally, IQUB showed a rescuing effect on the overlong cilia observed in ARL3T31A/C118F fibroblasts. Our results not only enhance our understanding of ARL3-related diseases but also provide new insights into the analysis of heterozygous and compound heterozygous mutations in genetics.

Pancreonecrosis as a complication of biliary pancreatitis in a child with morbid obesity

Obesity in children is often accompanied by organic and functional changes on the part of the organs of the hepatobiliary system and pancreas. The article describes a clinical case of complicated course of gastrointestinal tract and pancreatic steatosis on the background of morbid obesity in a 15-year-old child with the development of choledocholithiasis, in turn, complicated by acute pancreatitis, pancreonecrosis, peritonitis and perforation of the colon. The tactics of child management, a set of diagnostic methods of examination, methods of surgical treatment are described. The necessity of early detection of both obesity itself and timely screening of its complications and comorbid pathology to prevent potentially life-threatening conditions is shown. Ultrasound of the abdominal cavity and biochemical blood analysis are mandatory for obese children. In cases of unclear genesis of jaundice, MRI is recommended to exclude obturation and abnormalities of the biliary tract. The choice of surgical tactics for the treatment of children with GI, acute pancreatitis is determined by the combination of complications, the condition of the child and the results of laboratory-radiation research methods.

A 6-week randomized-controlled field study: effect of isokinetic eccentric resistance training on strength, flexibility and muscle structure of the shoulder external rotators in male junior handball players.

Background: Team handball involves a tremendous amount of shoulder motion with high forces during repeated extended external range of motion. This causes shoulder complaints and overuse injuries. While eccentric training for the lower extremity shows preventive effects by improving strength, range of motion and fascicle length, there is a research gap for the shoulder joint and for advanced tissue characterization using diffusion tensor imaging. Objectives: To investigate the effects of 6-week eccentric isokinetic resistance training on strength, flexibility, and fiber architecture characteristics of the external rotators compared to an active control group in junior male handball players. Methods: 15 subjects were randomly assigned to the eccentric training group and 14 subjects to the active control group (conventional preventive training). Primary outcome measures were eccentric and concentric isokinetic strength of the external rotators, range of motion, and muscle fascicle length and fascicle volume. Results: The intervention group, showed significant changes in eccentric strength (+15%). The supraspinatus and infraspinatus muscles showed significant increases in fascicle length (+13% and +8%), and in fractional anisotropy (+9% and +6%), which were significantly different from the control group. Conclusion: Eccentric isokinetic training has a significant effect on the function and macroscopic structure of the shoulder external rotators in male junior handball players. While strength parameters and muscle structure improved, range of motion did not change. This research helps understanding the physiology of muscle and the role of eccentric training on shoulder function and muscle structure. Furthermore, DTI was found to be a promising tool for advanced tissue characterization, and the in vivo derived data can also serve as model input variables and as a possibility to extend existing ex-vivo muscle models. Future research is needed for functional and structural changes following convenient eccentric field exercises.

Condition of the cardiovascular system in Wistar rats with experimental renal dysfunction

The aim: to evaluate functional and structural changes in blood vessels and myocardium in Wistar rats at different stages of the formation of experimental kidney dysfunction.Materials and Methods. Four groups of animals were studied. The first two groups consisted of rats subjected to 5/6 nephrectomy (NE). The period after NE is 2 or 4 months. The third and fourth groups included sham-operated (SO) animals of a similar observation period. After the end of the experiment, blood pressure was measured in rats, the left ventricular mass index (LVMI) was calculated, a biochemical blood test, histological, immunohistochemical and electron microscopic examination of the myocardium were performed, and the contractile activity of the portal vein was recorded for a period of 2 months (in vitro).Results. 2 months after NE, an increase in blood pressure, LVMI, and a decrease in the autorhythmic contractile activity of the portal vein were detected in rats. At the histological level, thickening of cardiomyocytes and arterial vessel walls and the presence of perivascular fibrosis were noted. After 4 months, in rats with NE, the increase in blood pressure, cardiomyocyte hypertrophy and perivascular fibrosis progressed. The thickness of cardiomyocytes was 14.1±3.11 μm, which was significantly greater than in the group with NE for 2 months (12.5±1.5 μm; p=0.008). At this period of observation, electron microscopic examination revealed deintegration of myofibrils, disruption of myofibril stacking and z-disk structure, and changes in the shape of mitochondria. 2 months after NE, an increase in the area of open capillaries was detected in rats (1902.8±202.9 μm²) compared to the corresponding LO animals (730.4±58.2 μm²; p=0.000). As renal dysfunction develops, the capillary area tends to increase (2139.1±396.5 μm²; p =0.120).Conclusion. In Wistar rats with renal dysfunction, changes were detected not only in the level of blood pressure, but also in the functional activity of the intravenous fluid, as well as in the structural components of the myocardium – cardiomyocytes, stroma and blood vessels. The increase in myocardial mass at the histological level was manifested by a significant increase in the thickness of cardiomyocytes, the volume of connective tissue, and the thickness of the wall of arterial vessels, reaching a maximum value at a longer period after NE.