Chronic Pathological Processes Research Articles

Copper homeostasis dysregulation in respiratory diseases: a review of current knowledge.

Cu is an essential micronutrient for various physiological processes in almost all human cell types. Given the critical role of Cu in a wide range of cellular processes, the local concentrations of Cu and the cellular distribution of Cu transporter proteins in the lung are essential for maintaining a steady-state internal environment. Dysfunctional Cu metabolism or regulatory pathways can lead to an imbalance in Cu homeostasis in the lungs, affecting both acute and chronic pathological processes. Recent studies have identified a new form of Cu-dependent cell death called cuproptosis, which has generated renewed interest in the role of Cu homeostasis in diseases. Cuproptosis differs from other known cell death pathways. This occurs through the direct binding of Cu ions to lipoylated components of the tricarboxylic acid cycle during mitochondrial respiration, leading to the aggregation of lipoylated proteins and the subsequent downregulation of Fe-S cluster proteins, which causes toxic stress to the proteins and ultimately leads to cell death. Here, we discuss the impact of dysregulated Cu homeostasis on the pathogenesis of various respiratory diseases, including asthma, chronic obstructive pulmonary disease, idiopathic interstitial fibrosis, and lung cancer. We also discuss the therapeutic potential of targeting Cu. This study highlights the intricate interplay between copper, cellular processes, and respiratory health. Copper, while essential, must be carefully regulated to maintain the delicate balance between necessity and toxicity in living organisms. This review highlights the need to further investigate the precise mechanisms of copper interactions with infections and immune inflammation in the context of respiratory diseases and explore the potential of therapeutic strategies for copper, cuproptosis, and other related effects.

Клиническое значение интегральной регистрации маркеров эндотоксического иммунитета и колонизационной резистентности буккальных эпителиоцитов при рецидивирующем бронхите у подростков

Recurrent bronchitis (RB) occupies one of the key places in the structure of nonspecific diseases of the respiratory tract and remains a significant medical and social problem in healthcare. The purpose — to investigate and evaluate the clinical significance of integral registration of markers of endotoxic immunity and colonization resistance of buccal epithelial cells (BE) in RB in adolescents. Material and methods. The study included 117 children (12–17 years old), including 78 with RB — the main group, 29 with acute bronchitis (AB) — the comparison group and 23 conditionally healthy children — the control group. The analysis of anamnestic, clinical, paraclinical data, verification of etiologically significant viruses, registration of artificial colonization of buccal epithelial cells (BE), colonization index (CI), micro-LAL test were carried out. Statistical processing of the results was carried out using the SPSS program. Results. A significant difference in markers of colonization resistance and anti-endotoxin protection was revealed in recurrent inflammation in the respiratory tract in comparison with AB in peers. In RB, the initial degree of Candida albicans adhesion to BE was significantly higher in relation to AB (p = 0.0427) and upon discharge from the hospital did not reach normative values, being significantly different from patients with AB (p = 0.0391). The high index of artificial colonization indicates the activation of allochthonous flora and disruption of the microbiota in the oral cavity, which negatively affects the body reactivity. In patients with RB, the titer of antiglycolipid antibodies significantly decreased and in 75% the values did not return to normal, while in AB they did not differ from the control. High levels of endotoxin were noted in RB compared to AB (p = 0.0317). Such patients were diagnosed with a more severe course of the disease with symptoms of endogenous intoxication and a long hospitalization period. Using the method of correlation analysis, a high direct relationship was established between artificial colonization and endotoxin concentration (r = 0.71). The relationship between these parameters in AB was significantly less pronounced (r = 0.3). The results obtained indicate close integration and mutual modulation of the local oral immunity and antiendotoxin defense. Conclusion. Integral registration of the markers of reactivity of specific anti-endotoxin immunity and colonization resistance reflect the severe inflammatory process in the respiratory tract and predict the risk of a chronic pathological process in the bronchopulmonary system.

MTHFR mutation: Another unifying etiology of chronic overlapping pain conditions

Introduction and Objective:Chronic pelvic pain (CPP) is a heterogeneous condition with multiple etiologies. Better characterization and understanding of CPP will lead to new therapeutic options and individualization of care, especially in patients with chronic overlapping pain syndromes (COPCs), which increase complexity of diagnosis. In this study, we present 6 patients with COPC and complex CPP, non-focal exam, who tested negative for small fiber neuropathy but who reported a history of methylenetetrahydrofolate reductase (MTHFR) mutations, and retrospective review of 76 patients with MTHFR mutation. This study explores through literature review whether MTHFR mutations play a role in the pathogenesis of chronic pelvic pain and overlapping pain conditions in a subset of patients with COPCs. Methods:Study design included an observational study of 6 patients, a retrospective cross-sectional study of 76 patients, and a literature review. Patients at our institution who tested positive for MTHFR mutations were included in the study; most had been seen in the cardiology/hematology clinics due to the association of MTHFR with clotting disorders. Chart review was performed to identify the presence of pain syndromes and specifically CPP. A review of the literature was undertaken to form a hypothesis for mechanisms that could explain the association between MTHFR mutations and chronic overlapping pain syndromes. Results:Of 76 patients with MTHFR mutations seen primarily in non-pain focused cardiology visits, 30 (39%) had some form of pain syndrome documented, 11 of whom (14%) specifically had CPP. The review below suggests that MTHFR plays a role in the maintenance of nerve tissue and conductance, neural tube defects, and paresthesia. Literature review revealed that MTHFR mutations have been linked with chronic pain and pathological processes such as chronic migraine, interstitial cystitis/bladder pain syndrome, sequelae of chronic Lyme disease, and fibromyalgia. Conclusions:The etiology of chronic pelvic pain is complex. Multisystem pain extending beyond the pelvis complicates the differential diagnosis but suggests a systemic cause. MTHFR mutations may play a unifying role in a subset of chronic pelvic pain patients with concomitant chronic overlapping pain syndromes. The mutations may affect folate metabolism pathways in these patients and hinder the ability to maintain nerve fibers over time, leading to dereliction of pain signal conduction. Disturbance of these pathways may have a role in chronic overlapping pain syndromes and complex pelvic pain.

Physiotherapeutic methods in complex treatment of obesity

The purpose of this work was to conduct an analytical review of scientific sources from Russian and foreign literature that present modern information about the risk factors of obesity; the most effective methods of treatment and rehabilitation are described. Based on the studied material, the main directions in the therapy of obesity, i. e. invasive and non-invasive, were identified. The essential components of a comprehensive approach for successful therapy of this chronic pathological process, in the context of a healthy lifestyle, mandatory dietary therapy, and correction of concomitant pathology, are physiotherapeutic procedures, therapeutic physical exercise, and psychological training. Modern physiotherapeutic methods include balneotherapy, electrotherapy, cryotherapy, ozone therapy, shockwave therapy, and others. Physiotherapeutic procedures significantly improve metabolism and contribute to weight stabilization with subsequent gradual normalization of body mass. Preference, especially in pediatric practice, is given to non-invasive physiotherapeutic methods, which are maximally safe for children, demonstrably effective, well-tolerated, and have a general strengthening effect on the growing and developing organism.

Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions.

Mycobacterium leprae is the etiological agent of leprosy. Macrophages (Mφs) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of Mφ subpopulations, namely M1, M2, and M4, in the skin lesions of patients diagnosed with leprosy. Based on the database of treatment-naïve patients treated between 2015 and 2019 at the Department of Dermatology of the University of the State of Pará, Belém, routine clinical screening samples were identified. The monolabeling protocol was used for M1 macrophages (iNOS, IL-6, TNF-α) and M2 macrophages (IL-10, IL-13, CD163, Arginase 1, TGF-β, FGFb), and the double-labeling protocol was used for M4 macrophages (IL-6, MMP7, MRP8, TNF-α e CD68). To confirm the M4 macrophage lineage, double labeling of the monoclonal antibodies CD68 and MRP8 was also performed. Our results demonstrated a statistically significant difference for the M1 phenotype among the Virchowian (VV) (4.5 ± 1.3, p < 0.0001), Borderline (1.6 ± 0.4, p < 0.0001), and tuberculoid (TT) (12.5 ± 1.8, p < 0.0001) clinical forms of leprosy. Additionally, the M2 phenotype showed a statistically significant difference among the VV (12.5 ± 2.3, p < 0.0001), Borderline (1.3 ± 0.2, p < 0.0001), and TT (3.2 ± 0.7, p < 0.0001) forms. For the M4 phenotype, a statistically significant difference was observed in the VV (9.8 ± 1.7, p < 0.0001), Borderline (1.2 ± 0.2, p < 0.0001), and TT (2.6 ± 0.7, p < 0.0001) forms. A significant correlation was observed between the VV M1 and M4 (r = 0.8712; p = 0.0000) and between the VV M2 × TT M1 (r = 0.834; p = 0.0002) phenotypes. The M1 Mφs constituted the predominant Mφ subpopulation in the TT and Borderline forms of leprosy, whereas the M2 Mφs showed increased immunoexpression and M4 was the predominant Mφ phenotype in VV leprosy. These results confirm the relationship of the Mφ profile with chronic pathological processes of the inflammatory response in leprosy.

Клинические исследования у беременных: проблемы и решения

The article deals with the need of compulsory participation of pregnant women in clinical research of drugs. By the beginning of the 90‑s of the last century, the majority of drugs prescribed to women was characterized by unsubstantial evidence of effectiveness and safety for women. Moreover, pregnant women almost did not participate in clinical research. Though pregnancy is a dynamic condition that can be compared with itself only. Then supervisory bodies created some documents regulating compulsory participation of the population in the research of drugs. However, until now, women are not sufficiently involved in the research of new original drugs, and pregnant women do the same very rarely. Possible scenarios of participation of pregnant women in clinical research have been reviewed. In particular, research of drugs used in therapy of abnormal conditions associated with pregnancy; drugs to treat chronic and acute pathological processes not related to pregnancy, and when a woman gets pregnant during the research have been distinguished. The importance of inclusion of pregnant women into the trials of effectiveness and safety of drugs in the presence of socially significant diseases, including the ones found during COVID‑19 pandemics, is postulated.

Label-Free Imaging Techniques to Evaluate Metabolic Changes Caused by Toxic Liver Injury in PCLS.

Abuse with hepatotoxic agents is a major cause of acute liver failure. The search for new criteria indicating the acute or chronic pathological processes is still a challenging issue that requires the selection of effective tools and research models. Multiphoton microscopy with second harmonic generation (SHG) and fluorescence lifetime imaging microscopy (FLIM) are modern label-free methods of optical biomedical imaging for assessing the metabolic state of hepatocytes, therefore reflecting the functional state of the liver tissue. The aim of this work was to identify characteristic changes in the metabolic state of hepatocytes in precision-cut liver slices (PCLSs) under toxic damage by some of the most common toxins: ethanol, carbon tetrachloride (CCl4) and acetaminophen (APAP), commonly known as paracetamol. We have determined characteristic optical criteria for toxic liver damage, and these turn out to be specific for each toxic agent, reflecting the underlying pathological mechanisms of toxicity. The results obtained are consistent with standard methods of molecular and morphological analysis. Thus, our approach, based on optical biomedical imaging, is effective for intravital monitoring of the state of liver tissue in the case of toxic damage or even in cases of acute liver injury.

Dynamic equilibrium of cellular plasticity: The origin of diseases

Since its inception, cellular plasticity has undergone many iterations. Today we define it as the ability of mature, terminally differentiated cells to change their identity, meaning lineage change of the cells by transdifferentiation, dedifferentiation and reprogramming. This process does not involve a single DNA sequence change or a mutation. We now know that the behavior of a cell is profoundly affected by the surrounding environment. There is a perpetual pressure placed on the genetic expression of the cells. The external environment and specifically the microenvironment of the cells greatly influences the genotype. There is a never-ending dynamic interplay between the genotype and the phenotype. Incremental phenotypic adjustments are continuously occurring to yield improved cell survival. These changes are beneficial to the cells at a given moment. As the environmental condition declines, then more extensive phenotypic transformation (via transdifferentiation and dedifferentiation) can follow. When the cellular environment further deteriorates, cellular plasticity can trigger a pathologic sequence that eventually leads to cancers/diseases. These modifications are all part of an adaptive process that enhances the survival of the cells. They can offer short term advantages, but they can also lead to diseases. Oxygen level plays a pivotal role in the development of chronic diseases. Cellular response to hypoxia is mediated through hypoxia inducible factor (HIF). HIF is an oxygen sensor that is closely involved in the pathophysiologic adaptation to hypoxia. Our hypothesis centers on hypoxia as the major stressor initiating cellular plasticity and restoring normoxia is an essential step in the healing process. This theory could be tested using chronic pathological processes in animal models whereby achieving an adequate cellular oxygen level could improve or halt both plastic change and diseases.

Intestinal Bacteremia After Liver Transplantation is a Risk Factor for Recurrence of Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic progressive pathological process, related to inflammatory bowel disease and subsequent bacterial translocation. Liver transplantation (LT) is the only curative therapy, but outcomes are compromised by recurrence of PSC (rPSC). The aim of the study was to investigate a potential link between intestinal bacteremia, fucosyltransferase-2 (FUT2), and rPSC after LT. LT recipients with PSC (n = 81) or without PSC (n = 271) were analyzed for clinical outcomes and positive bacterial blood cultures. A link between bacteremia and the genetic variant of the FUT2 gene was investigated. The incidence of inflammatory bowel disease was significantly higher in PSC recipients but not associated with rPSC. Bacteremia occurred in 31% of PSC recipients. The incidence of rPSC was 37% and was significantly more common in patients with intestinal bacteremia versus no bacteremia (82% versus 30%; P = 0.003). The nonsecretor polymorphism of the FUT2 gene was identified as a genetic risk factor for both intestinal bacteremia and rPSC. Combined FUT2 genotype and intestinal bacteremia in recipients resulted in the highest risk for rPSC (hazard ratio, 15.3; P < 0.001). Thus, in this article, we showed that bacterial translocation is associated with rPSC after LT and related to the FUT2 nonsecretor status.

Acute Pain Have Strong Intensity

Acute pain is a normal and predictable physiological response to a stimulus caused by a surgical procedure, injury, or acute illness. Chronic pain is pathological pain that lasts longer than the usual time to heal an injury or treat a disease. The causes are chronic and irreversible pathological processes in body cells and organs or damage to the peripheral or central nervous system. Acute pain occurs within 0.1 seconds after irritation. Acute pain is of strong intensity and is caused by stimulation of pain receptors.

Confocal microscopy of the corneal nerve fibers

This article presents the results of confocal microscopy of the corneal nerve fibers (CNF). The transparency of the cornea provides a unique potential for in vivo visualization of thin unmyelinated nerve fibers at the level close to morphological study. Modern software eliminates the need for manual tracing of the confocal image fragments, allows objectifying the process of assessment of CNF structure based on quantitative indicators characterizing the length, density and tortuosity of the main nerve trunks. Clinical application of structural analysis of the CNF has two potential directions associated with immediate tasks of ophthalmology, as well as with interdisciplinary affairs. In terms of ophthalmology, this primarily concerns various surgical interventions potentially affecting the state of the cornea, and chronic pathological processes in the cornea of different nature. Such studies could analyze the degree of changes in the CNF, or the particularities of corneal reinnervation. The potential for interdisciplinary studies lies in using CNF as biomarkers of systemic polyneuropathies. Relative simplicity, high level of direct visualization of the thin nerve fibers, and the obtained results allow recommending corneal confocal microscopy as a tool for primary screening and consequent monitoring of neuropathies in addition to the conventional methods.

The Impact of Cytokines in Coronary Atherosclerotic Plaque: Current Therapeutic Approaches.

Coronary atherosclerosis is a chronic pathological process that involves inflammation together with endothelial dysfunction and lipoprotein dysregulation. Experimental studies during the past decades have established the role of inflammatory cytokines in coronary artery disease, namely interleukins (ILs), tumor necrosis factor (TNF)-α, interferon-γ, and chemokines. Moreover, their value as biomarkers in disease development and progression further enhance the validity of this interaction. Recently, cytokine-targeted treatment approaches have emerged as potential tools in the management of atherosclerotic disease. IL-1β, based on the results of the CANTOS trial, remains the most validated option in reducing the residual cardiovascular risk. Along the same line, colchicine was also proven efficacious in preventing major adverse cardiovascular events in large clinical trials of patients with acute and chronic coronary syndrome. Other commercially available agents targeting IL-6 (tocilizumab), TNF-α (etanercept, adalimumab, infliximab), or IL-1 receptor antagonist (anakinra) have mostly been assessed in the setting of other inflammatory diseases and further testing in atherosclerosis is required. In the future, potential targeting of the NLRP3 inflammasome, anti-inflammatory IL-10, or atherogenic chemokines could represent appealing options, provided that patient safety is proven to be of no concern.

Sex-dependent expression of neutrophil gelatinase-associated lipocalin in aortic stenosis

BackgroundAccumulating evidence suggest the existence of sex-related differences in the pathogenesis of aortic stenosis (AS) with inflammation, oxidative stress, fibrosis and calcification being over-represented in men. Neutrophil gelatinase-associated lipocalin (NGAL) is expressed in a myriad of tissues and cell types, and it is associated with acute and chronic pathological processes comprising inflammation, fibrosis or calcification. Sex-dependent signatures have been evidenced for NGAL which expression has been associated predominantly in males to metabolic and cardiovascular disorders. We aimed to analyse sex-related differences of NGAL in AS and its role in the inflammatory and fibrocalcific progression of AS.Methods and results220 (60.45% men) patients with severe AS elective for surgical aortic valve (AV) replacement were recruited. Immunohistochemistry revealed higher expression of NGAL in calcific areas of AVs and that was validated by qPCR in in 65 (60% men) donors. Valve interstitial cells (VICs) were a source of NGAL in these samples. Proteome profiler analyses evidenced higher expression of NGAL in men compared to women, and that was further validated by ELISA. NGAL expression in the AV was correlated with inflammation, oxidative stress, and osteogenic markers, as well as calcium score. The expression of NGAL, both intracellular and secreted (sNGAL), was significantly deregulated only in calcifying male-derived VICs. Depletion of intracellular NGAL in calcifying male-derived VICs was associated with pro-inflammatory profiles, dysbalanced matrix remodelling and pro-osteogenic profiles. Conversely, exogenous NGAL mediated inflammatory and dysbalanced matrix remodelling in calcifying VICs, and all that was prevented by the pharmacological blockade of NGAL.ConclusionsOwing to the over-expression of NGAL, the AV from men may be endowed with higher expression of inflammatory, oxidative stress, matrix remodelling and osteogenic markers supporting the progression of calcific AS phenotypes. The expression of NGAL in the VIC emerges as a potential therapeutic checkpoint, with its effects being potentially reverted by the pharmacological blockade of extracellular NGAL.

Physical Development and Puberty in Related Patients with Kindler Epidermolysis Bullosa: Case Study

Background. Kindler epidermolysis bullosa is orphan, autosomal recessive disease and it is one of the variants of congenital epidermolysis bullosa. Its severe course is characterized by high risk of multifactorial malnutrition, chronic inflammation due to recurrent secondary skin infections, and also bone metabolism disorders, what can lead to disorders in physical development and puberty in children. However, the effect of Kindler epidermolysis bullosa on patients’ physical development and puberty remains unexplored.Clinical case description. Family case of Kindler epidermolysis bullosa was presented in 13 and 12 years old patients, third degree of kinship (maternal, uncle — nephew) with typical clinical manifestations for this disease. The diagnosis was confirmed in both patients via Sanger sequencing and revealing identical pathogenic variants in the FERMT1 gene (two deletions in the compound-heterozygous state — c.778del, p.Q260Kfs*21 and c.1088del, p. L363Wfs*39). Reduced concentrations of testosterone and 25(OH)D were revealed, whereas, increased concentration of adrenocorticotropic hormone — only in the older patient. The concentrations of luteinizing hormone, follicle-stimulating hormone and estradiol in both patients were within the reference values. The younger patient had prepubertal sizes and volume of testicles. Both patients had specific features of psychoemotional state: mood swing with rapid increase in anxiety level in the older patient and difficulties in emotional-volitional regulation in younger one.Conclusion. Patients with Kindler epidermolysis bullosa have high risk of physical development and puberty delay due to its systemic chronic pathological process. Thus, these patients require dynamic follow-up by pediatrician and pediatric endocrinologist.

A micro-computed tomography study of the sinus tympani variation in humans.

The posterior part of the tympanic cavity comprises a depression called the sinus tympani (ST). The said structure is of outmost importance, e.g. in surgical procedures involving the middle ear, as a pathology (microbial biofilm or cholesteatoma) present in this difficult to access location might hinder its effective treatment. The aim of the study was to evaluate anatomical variants of the ST in human adult petrous bones. For this purpose, three-dimensional (3D) models of the ST were recreated from micro-computed tomography (CT) scans of 44 dry petrous bone samples (19 female, 25 male), applying 3D Slicer, Meshmixer and MeshLab software. Anatomical variants of the ST were classified in terms of both shape and surface configuration. The internal configuration of the ST was classified as heterogeneous - containing small bony trabeculae and crests up to 1.0 mm in size, contrasting to homogeneous ST that characterizes a relatively smooth interior, or mere presence of minor depressions and mild folds. Female STs were more bowl-shaped (57.9%) than saccular (42.1%), and had heterogeneous surface configuration (52.6%) compared to homogeneous (47.4%). On the contrary, male STs were more saccular (52.0%) rather than bowl-shaped (48.0%), and predominantly had a heterogeneous surface (84.0%) over homogeneous (16.0%). A complex combination of ST features comprised of a saccular shape and heterogeneous surface occurred in 52.0% of males and in 15.8% of females (a statistically significant difference; p = 0.0254, Fisher's exact test) seems to be clinically important because of its potential negative implication on health outcomes after surgery in the case of, for example, cholesteatoma, and it may also favour chronic pathological processes.

IL-1β blockade prevents cell death and mucosal damage of the small intestine in a model of sterile inflammation

The intestinal mucosa is covered by a layer of epithelial cells that is constantly challenged by commensal, opportunistic, and pathogenic microorganisms, their components, and harmful compounds. Any inflammatory response to these materials must be tightly controlled to limit tissue damage and restore the integrity of the mucosal barrier. We have shown previously that production of IL-1β via activation of the inflammasome can lead to mucosal damage in the small intestinal pathology that occurs after intragastric administration of a gluten derived peptide, p31–43. Here we show that specific inhibition of caspase-1 or NLRP3 abolishes the damage induced by p31–43, and that antibody-mediated blocking of IL-1β inhibits the both the histological changes and the induction of apoptosis and caspase-3 activation driven by p31–43. Understanding the role of IL-1β in sterile inflammation may help to understand chronic inflammatory pathological processes, and design new intervention strategies.

β-Elemene Attenuates Renal Fibrosis in the Unilateral Ureteral Obstruction Model by Inhibition of STAT3 and Smad3 Signaling via Suppressing MyD88 Expression.

Renal fibrosis is a chronic pathological process that seriously endangers human health. However, the current therapeutic options for this disease are extremely limited. Previous studies have shown that signaling factors such as JAK2/STAT3, Smad3, and Myd88 play a regulatory role in renal fibrosis, and β-elemene is a plant-derived sesquiterpenoid organic compound that has been shown to have anti-inflammatory, anti-cancer, and immunomodulatory effects. In the present study, the anti-fibrotic effect of β-elemene was demonstrated by in vivo and in vitro experiments. It was shown that β-elemene inhibited the synthesis of extracellular matrix-related proteins in unilateral ureteral obstruction mice, and TGF-β stimulated rat interstitial fibroblast cells, including α-smooth muscle actin, vimentin, and connective tissue growth factor, etc. Further experiments showed that β-elemene reduced the expression levels of the above-mentioned fibrosis-related proteins by blocking the phosphorylation of JAK2/STAT3, Smad3, and the expression or up-regulation of MyD88. Notably, knockdown of MyD88 attenuated the phosphorylation levels of STAT3 and Smad3 in TGF-β stimulated NRK49F cell, which may be a novel molecular mechanism by which β-elemene affects renal interstitial fibrosis. In conclusion, this study elucidated the anti-interstitial fibrosis effect of β-elemene, which provides a new direction for future research and development of drugs related to chronic kidney disease.

Where the central canal begins: endoscopic in vivo description.

Although evidence and descriptions of the central canal (CC) along the medulla oblongata and the spinal cord have been provided by several anatomical and radiological studies, a clear picture and assessment of the opening of the CC, or apertura canalis centralis (ACC), into the fourth ventricle is lacking, due to its submillimetric size and hidden position in the calamus scriptorius. The authors reviewed all of their cases in which patients underwent ventricular transaqueductal flexible endoscopic procedures and selected 44 cases in which an inspection of the region of the calamus scriptorius had been performed and was suitable for study inclusion. Patients were divided into different groups, based on the presence or absence of a chronic pathological process involving the fourth ventricle. In each case, the visual appearance of the opening of the CC of the ACC was classified as no evidence (A0), indirect evidence (A1), or clear evidence (A2). Morphometric measurements were inferred from surrounding structures and the size of surgical tools visible in the field. The opening of the CC could be clearly observed in all cases (A1 4.5%, A2 95.5%). In normal cases, a lanceolate shape along the median sulcus was most frequently found, with an average size of 600 × 250 µm that became rounded and smaller in size in cases of hydrocephalus. The distance between the caudal margin of the ACC and the obex was about 1.8 mm in normal cases, 2.1 mm in cases of obstructive hydrocephalus, and 1 mm in cases of normal pressure hydrocephalus. The two wings of the area postrema, variable in size and shape, were sited just caudal to the opening. A flexible scope inserted through the cerebral aqueduct can approach the hidden calamus scriptorius like a pen fits into an inkpot. With this privileged viewpoint, the authors provide for the first time, to their knowledge, a clear and novel vision of the opening of the CC in the fourth ventricle, along with the precise location of this tiny structure compared to other anatomical landmarks in the inferior triangle.

The Role of Helper T Cells in Psoriasis.

Psoriasis is a complex, chronic relapsing and inflammatory skin disorder with a prevalence of approximately 2% in the general population worldwide. Psoriasis can be triggered by infections, physical injury and certain drugs. The most common type of psoriasis is psoriasis vulgaris, which primarily features dry, well-demarcated, raised red lesions with adherent silvery scales on the skin and joints. Over the past few decades, scientific research has helped us reveal that innate and adaptive immune cells contribute to the chronic inflammatory pathological process of psoriasis. In particular, dysfunctional helper T cells (Th1, Th17, Th22, and Treg cells) are indispensable factors in psoriasis development. When stimulated by certain triggers, antigen-presenting cells (APCs) can release pro-inflammatory factors (IL-23, IFN-α and IL-12), which further activate naive T cells and polarize them into distinct helper T cell subsets that produce numerous cytokines, such as TNF, IFN-γ, IL-17 and IL-22, which act on keratinocytes to amplify psoriatic inflammation. In this review, we describe the function of helper T cells in psoriasis and summarize currently targeted anti-psoriatic therapies.

Погляд спортивного травматолога на біомеханіку кульшового суглоба

Як основна ланка між верхньою частиною тіла та нижньою кінцівкою кульшовий суглоб відіграє важливу роль у розвитку та передачі імпульсів сили під час виконання щоденних рутинних дій та спортивних вправ. Для цього суглоба характерний надзвичайно високий рівень природної кісткової стійкості, а особливості його кісткової структури значно впливають на його біомеханічні властивості. Ці біомеханічні принципи мають велике значення при встановленні діагнозу та показань до оперативного лікування структурних аномалій кульшового суглоба, а також для розуміння фізичних навантажень на кульшовий суглоб під час спортивних тренувань, які можуть призвести до травм або хронічних патологічних процесів.