ABSTRACT
The future of therapy for neurodegenerative diseases (NDs) relies on new strategies targeting multiple pharmacological pathways. Our research led to obtaining the compound AR71 [(E)-3-(3,4,5-trimethoxyphenyl)-1-(4-(3-(piperidin-1-yl)propoxy)phenyl)prop-2-en-1-one], which has high affinity for human H3R (Ki = 24 nM) and selectivity towards histamine H1 and H4 receptors (Ki > 2500 nM), and showed anti-inflammatory activity in a model of lipopolysaccharide-induced inflammation in BV-2 cells. The presented tests confirmed its antagonist/inverse agonist activity profile and good metabolic stability while docking studies showed the binding mode to histamine H1, H3, and H4 receptors. In in vitro tests, cytotoxicity was evaluated at three cell lines (neuroblastoma, astrocytes, and human peripheral blood mononuclear cells), and a neuroprotective effect was observed in rotenone-induced toxicity. In vivo experiments in a mouse neuropathic pain model demonstrated the highest analgesic effects of AR71 at the dose of 20 mg/kg body weight. Additionally, AR71 showed antiproliferative activity in higher concentrations. These findings suggest the need for further evaluation of AR71's therapeutic potential in treating ND and CNS cancer using animal experimental models.
Subject(s)
Analgesics , Anti-Inflammatory Agents , Receptors, Histamine H3 , Animals , Humans , Mice , Receptors, Histamine H3/metabolism , Analgesics/pharmacology , Anti-Inflammatory Agents/pharmacology , Ligands , Molecular Docking Simulation , Male , Neuralgia/drug therapy , Neuralgia/metabolism , Neuralgia/chemically induced , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Lipopolysaccharides , Cell Line, TumorABSTRACT
OBJECTIVE: This pilot study sought to investigate the utility and acceptability of the KardiaMobile 6-lead ECG (KM6LECG) as a tool for remote monitoring in children with inherited cardiac conditions. DESIGN: A single-centre prospective cohort study. Children underwent standard clinical evaluation including a 12-lead ECG and a KM6LECG in the clinic. Participants recorded KM6LECGs monthly at home for 3 months. Families completed a questionnaire on their experience. SETTING: Great Ormond Street Hospital Centre for Inherited Cardiovascular Diseases. PARTICIPANTS: 64 children: 22 with hypertrophic cardiomyopathy (HCM); 22 with long QT syndrome and 20 unaffected siblings (controls). MAIN OUTCOME MEASURES: Comparison of data extracted from the clinic 12-lead ECG and supervised KM6LECG, and the supervised and unsupervised KM6LECG recording. RESULTS: Of 64 children (35% female, mean age 12 years), 58 had a baseline 12-lead ECG and appropriate baseline KM6LECG. In children with HCM, abnormalities in ventricular depolarisation/repolarisation in the limb leads of the 12-lead ECG were reliably reproduced. From the whole cohort, there was a strong positive correlation between the corrected QT interval from the 12-lead ECG and baseline KM6LECG (intraclass correlation coefficient=0.839) and baseline KM6LECG with an unsupervised KM6LECG (intraclass correlation coefficient=0.736). Suspected 'lead' misplacement impacted 18% of unsupervised recordings. Overall, the acceptability of the KM6LECG to families was good. CONCLUSIONS: The KM6LECG provides an accurate tool for assessing some ECG abnormalities associated with paediatric inherited cardiovascular disease and may provide a useful at-home adjunct to face-to-face clinical care of children requiring ECG assessment.
Subject(s)
Long QT Syndrome , Humans , Female , Male , Child , Prospective Studies , Pilot Projects , Long QT Syndrome/diagnosis , Adolescent , Electrocardiography/methods , Cardiomyopathy, Hypertrophic/diagnosis , Cardiomyopathy, Hypertrophic/physiopathology , Child, Preschool , Patient Acceptance of Health Care/statistics & numerical dataABSTRACT
In these studies, we designed and investigated the potential anticancer activity of five iron(II) cyclopentadienyl complexes bearing different phosphine and phosphite ligands. All complexes were characterized with spectroscopic analysis viz. NMR, FT-IR, ESI-MS, UV-Vis, fluorescence, XRD (for four complexes) and elemental analyses. For biological studies, we used three types of cells-normal peripheral blood mononuclear (PBM) cells, leukemic HL-60 cells and non-small-cell lung cancer A549 cells. We evaluated cell viability and DNA damage after cell incubation with these complexes. We observed that all iron(II) complexes were more cytotoxic for HL-60 cells than for A549 cells. The complex CpFe(CO)(P(OPh)3)(η1-N-maleimidato) 3b was the most cytotoxic with IC50 = 9.09 µM in HL-60 cells, IC50 = 19.16 µM in A549 and IC50 = 5.80 µM in PBM cells. The complex CpFe(CO)(P(Fu)3)(η1-N-maleimidato) 2b was cytotoxic only for both cancer cell lines, with IC50 = 10.03 µM in HL-60 cells and IC50 = 73.54 µM in A549 cells. We also found the genotoxic potential of the complex 2b in both types of cancer cells. However, the complex CpFe(CO)2(η1-N-maleimidato) 1 which we studied previously, was much more genotoxic than complex 2b, especially for A549 cells. The plasmid relaxation assay showed that iron(II) complexes do not induce strand breaks in fully paired ds-DNA. The DNA titration experiment showed no intercalation of complex 2b into DNA. Molecular docking revealed however that complexes CpFe(CO)(PPh3) (η1-N-maleimidato) 2a, 2b, 3b and CpFe(CO)(P(OiPr)3)(η1-N-maleimidato) 3c have the greatest potential to bind to mismatched DNA. Our studies demonstrated that the iron(II) complex 1 and 2b are the most interesting compounds in terms of selective cytotoxic action against cancer cells. However, the cellular mechanism of their anticancer activity requires further research.
Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Coordination Complexes , Lung Neoplasms , Phosphines , Phosphites , Humans , Molecular Docking Simulation , Coordination Complexes/chemistry , Iron , Leukocytes, Mononuclear/metabolism , Spectroscopy, Fourier Transform Infrared , DNA/metabolism , Maleimides , Ferrous Compounds/pharmacology , Antineoplastic Agents/chemistry , Ligands , Cell Line, TumorABSTRACT
The aim of this study was to assess the long-term results of liver transplantation (LT) in pediatric patients with unresectable hepatoblastoma (HB) or hepatocellular carcinoma (HCC) with special reference to the risk of tumor recurrence. We retrospectively analyzed data from 46 HB and 26 HCC patients who underwent LT between 1990 and 2022. In HCC patients, we compared outcomes depending on donor type. We evaluated the impact of a number of risk factors on recurrence-free survival after LT. Estimated patient survival after 5, 10, and 15 years was 82%, 73%, and 73% in the HB group and 79%, 75%, and 75% in the HCC group, respectively (p = 0.76). In the HCC group, living donor LT (LDLT) and deceased donor LT (DDLT) provided similar patient survival (p = 0.09). Estimated recurrence-free survival in patients who had three or fewer risk factors was significantly better than in patients with more than three risk factors (p = 0.0001). Adequate patient selection is necessary when considering LT for primary liver tumors in children. The presence of more than three risk factors is associated with a very high risk of recurrence and indicates poor prognosis, whereas extrahepatic disease may be considered a contraindication for transplantation.
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Background and objectives: X-linked adrenomyeloneuropathy (AMN) is an inherited neurodegenerative disorder associated with mutations in the ABCD1 gene and the accumulation of very long-chain fatty acids (VLFCAs) in plasma and tissues. Currently, there is no effective treatment for AMN. We have aimed to evaluate the therapeutic effects of mesenchymal stem cell (MSC) transplantation in patients with AMN. Methods: This is a small cohort open-label study with patients with AMN diagnosed and treated at the University Hospital in Olsztyn, Poland. All patients met clinical, biochemical, MRI, and neuropsychological criteria for AMN. MSCs derived from Wharton jelly, 20 × 106 cells, were administered intrathecally three times every 2 months, and patients were followed up for an additional 3 months. The primary outcome measures included a blinded assessment of lower limb muscle strength with the Medical Research Council Manual Muscle Testing scale at baseline and on every month visits until the end of the study. Additional outcomes included measurements of the timed 25-feet walk (T25FW) and VLFCA serum ratio. Results: Three male patients with AMN with an age range of 26-37 years participated in this study. All patients experienced increased muscle strength in the lower limbs at the end of the study versus baseline. The power grade increased by 25-43% at the baseline. In addition, all patients showed an improvement trend in walking speed measured with the T25FW test. Treatment with MSCs in patients with AMN appeared to be safe and well tolerated. Discussion: The results of this study demonstrated that intrathecal administration of WJ-MSC improves motor symptoms in patients with AMN. The current findings lend support to the safety and feasibility of MSC therapy as a potentially viable treatment option for patients with AMN.
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Current treatments of degenerated intervertebral discs often provide only temporary relief or address specific causes, necessitating the exploration of alternative therapies. Cell-based regenerative approaches showed promise in many clinical trials, but limitations such as cell death during injection and a harsh disk environment hinder their effectiveness. Injectable microscaffolds offer a solution by providing a supportive microenvironment for cell delivery and enhancing bioactivity. This study evaluated the safety and feasibility of electrospun nanofibrous microscaffolds modified with chitosan (CH) and chondroitin sulfate (CS) for treating degenerated NP tissue in a large animal model. The microscaffolds facilitated cell attachment and acted as an effective delivery system, preventing cell leakage under a high disc pressure. Combining microscaffolds with bone marrow-derived mesenchymal stromal cells demonstrated no cytotoxic effects and proliferation over the entire microscaffolds. The administration of cells attached to microscaffolds into the NP positively influenced the regeneration process of the intervertebral disc. Injectable poly(l-lactide-co-glycolide) and poly(l-lactide) microscaffolds enriched with CH or CS, having a fibrous structure, showed the potential to promote intervertebral disc regeneration. These features collectively address critical challenges in the fields of tissue engineering and regenerative medicine, particularly in the context of intervertebral disc degeneration.
Subject(s)
Chitosan , Intervertebral Disc Degeneration , Intervertebral Disc , Mesenchymal Stem Cells , Animals , Intervertebral Disc Degeneration/therapy , Tissue Engineering , Chondroitin Sulfates/metabolism , Chitosan/metabolismABSTRACT
Introduction: Mucous membrane pemphigoid (MMP) is diagnosed on the basis of a characteristic clinical picture (a predilection for mucosal involvement and scarring in the affected tissues) and a positive direct immunofluorescence (DIF) result. Methods: In this study, we compare the diagnostic and prognostic values of conjunctival and oral biopsies analyzed by DIF in patients with MMP. Sixteen patients with MMP and mucosal involvement as a predominant symptom were classified into three groups based on the clinical picture. Oral and conjunctival DIF were performed on all patients. Results: Our study showed that patients with simultaneous oral and conjunctival involvement had a positive oral DIF in 83% and a positive ocular DIF in 100% of the examined cases, respectively. Patients with isolated ocular MMP had a positive oral DIF in 50% and a positive ocular DIF in 66% of the examined cases, respectively. Patients with only oral involvement with MMP had a positive oral DIF in 100% and a positive ocular DIF in 50% of the examined cases, respectively. Discussion: Oral biopsy should be performed first and is usually sufficient for the diagnosis, even in patients with exclusively ocular MMP, whereas in patients without clinical ocular involvement, ocular DIF is positive in half of the cases and may be a predictive factor for ocular lesions in the future.
ABSTRACT
Epidermolysis bullosa acquisita (EBA) is a chronic, recurrent autoimmune subepidermal bullous disease characterized by the presence of autoantibodies targeting type VII collagen -- basement membrane zone antigen. Standard therapy for EBA includes a combination of systemic corticosteroids and dapsone; however, severe cases may require advanced treatment. The current article reports on four EBA cases in which biologics: infliximab, rituximab (Rtx), and intravenous immunoglobulin (IVIG) were applied. All patients fulfilled the clinical and immunological criteria of EBA: they presented tense blisters healing with atrophic scars on the skin on traumatized areas and in mucous membranes. The diagnosis of EBA was established using numerous techniques: direct and indirect immunofluorescence, salt split skin, ELISA, Fluorescence Overlay Antigen Mapping using Laser Scanning Confocal Microscopy. Since all the patients did not achieve long-term remission on standard treatment (prednisone, dapsone) due to ineffectiveness or side effects of drugs, they eventually were treated with biologics leading to extraordinary skin improvement and stopping the disease for 1-3 years. Biologics in all patients were tolerated very well. No side effects were observed during application as well as multi-month follow-up. The presented cases provide a premise that biological drugs can be a valuable component of EBA therapy.
Subject(s)
Biological Products , Epidermolysis Bullosa Acquisita , Humans , Epidermolysis Bullosa Acquisita/diagnosis , Epidermolysis Bullosa Acquisita/drug therapy , Blister , Autoantibodies , Dapsone/therapeutic use , Biological Products/therapeutic useABSTRACT
Loricrin keratoderma (LK) is a rare autosomal dominant genodermatosis caused by LORICRIN gene mutations. The pathogenesis of the disease is not yet fully understood. So far, only 10 pathogenic variants in LORICRIN have been described, with all of them but one being deletions or insertions. The significance of rare nonsense variants remains unclear. Furthermore, no data regarding the RNA expression in affected patients are available. The aim of this study is to describe the two variants in the LORICRIN gene found in two distinct families: the novel pathogenic variant c.639_642dup and a rare c.10C > T (p.Gln4Ter) of unknown significance. We also present the results of the transcriptome analysis of the lesional loricrin keratoderma epidermis of a patient with c.639_642dup. We show that in the LK lesion, the genes associated with epidermis development and keratocyte differentiation are upregulated, while genes engaged in cell adhesion, differentiation developmental processes, ion homeostasis and transport, signaling and cell communication are downregulated. In the context of the p.Gln4Ter clinical significance evaluation, we provide data indicating that LORICRIN haploinsufficiency has no skin consequences. Our results give further insight into the pathogenesis of LK, which may have therapeutic implications in the future and important significance in the context of genetic counseling.
Subject(s)
Skin Diseases, Genetic , Humans , Skin Diseases, Genetic/metabolism , Epidermis/metabolism , Gene Expression ProfilingABSTRACT
Most naturally occurring nucleotides and nucleosides are N-glycosyl derivatives of ß-d-ribose. These N-ribosides are involved in most metabolic processes that occur in cells. They are essential components of nucleic acids, forming the basis for genetic information storage and flow. Moreover, these compounds are involved in numerous catalytic processes, including chemical energy production and storage, in which they serve as cofactors or coribozymes. From a chemical point of view, the overall structure of nucleotides and nucleosides is very similar and simple. However, their unique chemical and structural features render these compounds versatile building blocks that are crucial for life processes in all known organisms. Notably, the universal function of these compounds in encoding genetic information and cellular catalysis strongly suggests their essential role in the origins of life. In this review, we summarize major issues related to the role of N-ribosides in biological systems, especially in the context of the origin of life and its further evolution, through the RNA-based World(s), toward the life we observe today. We also discuss possible reasons why life has arisen from derivatives of ß-d-ribofuranose instead of compounds based on other sugar moieties.
Subject(s)
Nucleic Acids , Nucleosides , Nucleosides/chemistry , Nucleotides , RNA/chemistry , CatalysisABSTRACT
It is known that phenolic compounds can alleviate the negative impact of oxidative stress and modulate hemostasis. However, the effect of extracts and phenolics from Glechoma hederacea L. on the biomarkers of these processes is not well documented. The aim of our study was to investigate the in vitro protective effects of one extract and three fractions (20, 60, and 85% fraction) from G. hederacea L. on oxidative stress and hemostasis. Phytochemical analysis showed that aerial parts of G. hederacea L. are rich in both phenolic acids (such as rosmarinic acid, neochlorogenic acid, and chlorogenic acid) and flavonoids (mainly rutin and glycoside derivatives of apigenin, quercetin, and luteolin). We observed that the 85% fraction (at three concentrations: 5, 10, and 50 µg/mL) inhibited protein carbonylation. Moreover, the extract and 85% fraction (at the concentration of 50 µg/mL) could reduce lipid peroxidation. All fractions and the extract were very effective at decreasing H2O2-induced DNA damage in PBM cells. The 85% fraction had the strongest protective potential against DNA oxidative damage. We also observed that the extract and fractions decreased PBM cell viability to a maximum of 65% after 24 h incubation. Our results indicate that the 85% fraction showed the strongest antioxidant potential. The main component of the 85% fraction was apigenin (26.17 ± 1.44 mg/g), which is most likely responsible for its strong antioxidant properties.
Subject(s)
Antioxidants , Lamiaceae , Humans , Antioxidants/pharmacology , Antioxidants/chemistry , Hydrogen Peroxide/toxicity , Apigenin , Plant Extracts/pharmacology , Plant Extracts/chemistry , Anticoagulants/pharmacology , Anticoagulants/chemistry , Lamiaceae/chemistry , Phytochemicals/pharmacologyABSTRACT
In these studies, we designed and investigated cyto- and genotoxic potential of five ruthenium cyclopentadienyl complexes bearing different phosphine and phosphite ligands. All of the complexes were characterized with spectroscopic analysis (NMR, FT-IR, ESI-MS, UV-vis, fluorescence and XRD (for two compounds)). For biological studies, we used three types of cells - normal peripheral blood mononuclear (PBM) cells, leukemic HL-60 cells and doxorubicin-resistance HL-60 cells (HL-60/DR). We compared the results obtained with those obtained for the complex with maleimide ligand CpRu(CO)2(η1-N-maleimidato) 1, which we had previously reported. We observed that the complexes CpRu(CO)(PPh3)(η1-N-maleimidato) 2a and CpRu(CO)(P(OEt)3)(η1-N-maleimidato) 3a were the most cytotoxic for HL-60 cells and non-cytotoxic for normal PBM cells. However, complex 1 was more cytotoxic for HL-60 cells than complexes 2a and 3a (IC50 = 6.39 µM vs. IC50 = 21.48 µM and IC50 = 12.25 µM, respectively). The complex CpRu(CO)(P(OPh)3)(η1-N-maleimidato) 3b is the most cytotoxic for HL-60/DR cells (IC50 = 104.35 µM). We found the genotoxic potential of complexes 2a and 3a only in HL-60 cells. These complexes also induced apoptosis in HL-60 cells. Docking studies showed that complexes 2a and CpRu(CO)(P(Fu)3)(η1-N-maleimidato) 2b have a small ability to degrade DNA, but they may cause a defect in DNA damage repair mechanisms leading to cell death. This hypothesis is corroborated with the results obtained in the plasmid relaxation assay in which ruthenium complexes bearing phosphine and phosphite ligands induce DNA breaks.
Subject(s)
Antineoplastic Agents , Coordination Complexes , Neoplasms , Phosphites , Ruthenium , Humans , Ruthenium/pharmacology , Ruthenium/chemistry , Ligands , Leukocytes, Mononuclear , Spectroscopy, Fourier Transform Infrared , Maleimides/pharmacology , Coordination Complexes/chemistry , Antineoplastic Agents/chemistry , Cell Line, TumorABSTRACT
BACKGROUND: Paraneoplastic pemphigus (PNP), also called paraneoplastic autoimmune multiorgan syndrome (PAMS), is a rare autoimmune disease with mucocutaneous and multi-organ involvement. PNP/PAMS is typically associated with lymphoproliferative or haematological malignancies, and less frequently with solid malignancies. The mortality rate of PNP/PAMS is elevated owing to the increased risk of severe infections and disease-associated complications, such as bronchiolitis obliterans. OBJECTIVES: These guidelines summarize evidence-based and expert-based recommendations (S2k level) for the clinical characterization, diagnosis and management of PNP/PAMS. They have been initiated by the Task Force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology with the contribution of physicians from all relevant disciplines. The degree of consent among all task force members was included. RESULTS: Chronic severe mucositis and polymorphic skin lesions are clue clinical characteristics of PNP/PAMS. A complete assessment of the patient with suspected PNP/PAMS, requiring histopathological study and immunopathological investigations, including direct and indirect immunofluorescence, ELISA and, where available, immunoblotting/immunoprecipitation, is recommended to achieve a diagnosis of PNP/PAMS. Detection of anti-envoplakin antibodies and/or circulating antibodies binding to the rat bladder epithelium at indirect immunofluorescence is the most specific tool for the diagnosis of PNP/PAMS in a patient with compatible clinical and anamnestic features. Treatment of PNP/PAMS is highly challenging. Systemic steroids up to 1.5 mg/kg/day are recommended as first-line option. Rituximab is also recommended in patients with PNP/PAMS secondary to lymphoproliferative conditions but might also be considered in cases of PNP/PAMS associated with solid tumours. A multidisciplinary approach involving pneumologists, ophthalmologists and onco-haematologists is recommended for optimal management of the patients. CONCLUSIONS: These are the first European guidelines for the diagnosis and management of PNP/PAMS. Diagnostic criteria and therapeutic recommendations will require further validation by prospective studies.
Subject(s)
Paraneoplastic Syndromes, Nervous System , Paraneoplastic Syndromes , Animals , Rats , Autoimmune Diseases , Neoplasms/complications , Paraneoplastic Syndromes/diagnosis , Paraneoplastic Syndromes/etiology , Paraneoplastic Syndromes/therapy , Paraneoplastic Syndromes, Nervous System/diagnosis , Paraneoplastic Syndromes, Nervous System/etiology , Paraneoplastic Syndromes, Nervous System/therapy , Societies, MedicalABSTRACT
Although clinical trials on human neural stem cells (hNSCs) have already been implemented in the treatment of neurological diseases and they have demonstrated their therapeutic effects, many questions remain in the field of preclinical research regarding the biology of these cells, their therapeutic properties, and their neurorestorative potential. Unfortunately, scientific reports are inconsistent and much of the NSCs research has been conducted on rodents rather than human cells for ethical reasons or due to insufficient cell material. Therefore, a question arises as to whether or which conclusions drawn on the isolation, cell survival, proliferation, or cell fate observed in vitro in rodent NSCs can be introduced into clinical applications. This paper presents the effects of different spatial, nutritional, and dissociation conditions on NSCs' functional properties, which are highly species-dependent. Our study confirmed that the discrepancies in the available literature on NSCs survival, proliferation, and fate did not only depend on intra-species factors and applied environmental conditions, but they were also affected by significant inter-species variability. Human and rodent NSCs share one feature, i.e., the necessity to be cultured immediately after isolation, which significantly maintains their survival. Additionally, in the absence of experiments on human cells, rat NSCs biology (neurosphere formation potential and neural differentiation stage) seems closer to that of humans rather than mice in response to environmental factors.
Subject(s)
Neural Stem Cells , Rats , Mice , Humans , Animals , Cells, Cultured , Cell Differentiation , Cryopreservation , BiologyABSTRACT
A choledochal cyst is a rare malformation primarily diagnosed in children. The only effective therapy remains surgical cyst resection followed by Roux-en-Y hepaticojejunostomy. Treating asymptomatic neonates remains a point of discussion. Between 1984 and 2021, we performed choledochal cyst (CC) excision in 256 children at our center. Out of this group, we retrospectively reviewed the medical records of 59 patients who were operated on under one year of age. Follow-up ranged from 0.3 to 18 years (median 3.9 years). The preoperative course was asymptomatic in 22 (38%), while 37 patients (62%) had symptoms before surgery. The late postoperative course was uneventful in 45 patients (76%). In symptomatic patients, 16% had late complications, while in asymptomatic patients, only 4%. Late complications were observed in the laparotomy group in seven patients (17%). We did not observe late complications in the laparoscopy group. Early surgical intervention is not followed by a high risk of complications and may prevent the onset of preoperative complications, giving excellent early and long-term results, especially after minimally invasive laparoscopic surgery.
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OBJECTIVE: Cognitive impairment constitutes one of the major risk factors of delirium after coronary artery bypass graft (CABG) surgery; however, it is unclear whether only patients with global cognitive decline are at increased risk for delirium or if individuals with preserved global cognitive functions but impairments in specific cognitive domains are also more vulnerable to developing delirium. Thus, this study aimed to analyze the neurocognitive status of patients scheduled for CABG surgery with the use of an advanced computerized cognitive battery (CNS Vital Signs) and to investigate possible associations between impaired performance in selective cognitive areas and the risk of postoperative delirium development. METHODS: The study enrolled 127 participants with a median age of 67 years (IQR: 63-71). Postoperative delirium developed in 32 (25%) patients.Before surgery, the patients were screened for global cognitive impairment with the use of the Mini-Mental State Examination Test, and the individuals were asked to perform the CNS Vital Signs battery to investigate 12 specific cognitive domains. The Confusion Assessment Method and the Memorial Delirium Assessment Scale were used to screen for a diagnosis of delirium postoperatively. RESULTS: In multivariate models, a lower score of verbal memory-assessed preoperatively was independently associated with the risk of postoperative delirium development. Other independent predictors of delirium included more advanced age, gender female, depression, postoperative pyrexia, and the presence of extracorporeal circulation. CONCLUSIONS: As decreased verbal memory constitutes an independent risk factor for postoperative delirium, a verbal memory test may be a useful predictor of postoperative delirium development.
Subject(s)
Delirium , Emergence Delirium , Humans , Female , Middle Aged , Aged , Prospective Studies , Delirium/diagnosis , Delirium/etiology , Delirium/psychology , Emergence Delirium/complications , Neuropsychological Tests , Postoperative Complications/etiology , Postoperative Complications/diagnosis , Postoperative Complications/psychology , Coronary Artery Bypass/adverse effects , Cognition , Risk FactorsABSTRACT
BACKGROUND: Premature ventricular contractions (PVCs) are frequently seen in children and are considered benign. A substantial group of adolescents with PVCs complain about a broad range of clinical symptoms, including low exertion tolerance. OBJECTIVE: The purpose of this study was to evaluate prospectively whether ventricular arrhythmia affects physical performance in adolescents with normal left ventricular function, using a cardiopulmonary exercise test (CPET) and evaluating the electrocardiographic (ECG) characteristics of patients with PVCs with regard to exercise capacity. METHODS: The study group consisted of 49 children with PVCs and normal left ventricular function. The control group consisted of 36 healthy volunteers. Standard ECG, 24-hour Holter ECG, and CPET were performed. PVCs were analyzed for QRS duration, bundle branch block pattern, QRS axis, and coupling interval (CInt). For CPET, heart rate (HR), oxygen uptake (VO2max), predicted VO2max, and VO2max expressed as a percentage of the predicted value (%VO2) were measured. RESULTS: In 37 patients (76%), arrhythmia subsided during exercise. Patients achieved lower VO2max (32.9 ± 6.3 mL/min/kg) than controls (40.4 ± 6.7 mL/min/kg; P <.01). %VO2 was 71.0 ± 13.7 in patients and 79.3 ± 12.2 in controls (P <.01). Exercise HR at which PVCs subsided correlated with VO2max (r = 0.3; P = .07). Patients with persisting arrhythmia performed worse than those in whom arrhythmia subsided during exercise (VO2max, P <.01; %VO2,P <.01). No correlation between QRS and CInt parameters and VO2max was observed. CONCLUSION: Patients with PVCs have lower aerobic capacity than their healthy peers. Further worsening of exercise capacity is present when PVCs are preserved during effort.
Subject(s)
Ventricular Premature Complexes , Adolescent , Humans , Child , Ventricular Premature Complexes/diagnosis , Electrocardiography , Exercise Test , Heart Rate , Bundle-Branch Block/diagnosisABSTRACT
Cardiomyopathies have a low prevalence in children and thus may lead to malignant ventricular arrhythmias or the progression of heart failure, resulting in death. In adults, the QRS-T angle derived from ECG has been associated with adverse outcomes in patients with hypertrophic and dilated cardiomyopathies. We aimed to assess the electrocardiographic parameters, including QRS-T angle, associated with adverse cardiac events in children with cardiomyopathies. Forty-two children with cardiomyopathies were included in this study: 19 with dilated cardiomyopathy, 17 with hypertrophic cardiomyopathy, and 6 with left ventricular non-compaction. Additionally, 19 control subjects were recruited. In terms of ECG parameters, the QRS-T angle was significantly greater among patients with adverse outcomes compared to patients without the end points of the study (133° vs. 65°, p < 0.001). On Kaplan−Meier survival curves, QRS-T angle > 120°, increased serum concentrations of NT-proBNP and troponin I levels as well as greater NYHA or Ross scale were associated with the greatest risk of unfavorable outcome. The QRS-T angle appears to be a valuable component of 12-lead ECG interpretation, and might be helpful in outlining patients with the greatest cardiovascular risk. Additionally, serum biomarkers such as NT-proBNP (p = 0.003) and troponin (p < 0.001) are useful in outlining patients with the worst survival.
ABSTRACT
Plastic can be used for many things and at the same time is the most versatile material in our modern world. However, the uncontrolled and unprecedented use of plastic comes to its end. The global ban on plastic brings significant changes in technology but even more so in civil perception-changes taking place before our eyes. The aim of this study was to find answers to the questions about the readiness of consumers for a global ban on plastic. Within the research, the differences in consumer acceptance in countries in Europe, South and North America and Asia and the expression of social readiness to change attitudes towards plastic food packaging were analyzed. This work sketches the legal framework related to limiting the use of one-use food packaging made of fossil raw materials at the level of the European Union, Poland and Portugal but also at the level of the two largest economies in the world, China and the United States, as well as lower-income countries, e.g., Ukraine and Brazil. The survey results were analyzed using descriptive and inferential statistics. The performed study demonstrates that, in in all the surveyed countries, appropriate legal acts related to the reduction of plastic in everyday life are already in place. Furthermore, this work demonstrates the full understanding of plastic banning in all surveyed countries. Consumers are aware that every effort should be made to prevent the world from drowning in plastic waste. Society is, in general, open to the use of bioplastics produced from the second-generation resource if second-generation bioplastics contribute to environmental and pollution reduction targets.