Cardio-Oncoimmunology: Cardiac Toxicity, Cardiovascular Hypersensitivity, and Kounis Syndrome.

Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT prolongation, torsades de pointes, pericardial effusion, and hypotension, as well as chronic conditions, such as hypertension, and systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovascular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovascular side effect continues even after the causative medication is stopped, it is referred to as a cardiotoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even at very low medication dosages, and can present as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome, and myocarditis caused by cancer therapy.

Evidence of Language Development Using Brief Animated Stimuli: A Systematic Review.

There is limited evidence regarding the effect of animation compared to static pictures on children's language development. The aim was to systematically review the available literature for evidence concerning the effect of brief animation on spoken language responses (receptive-listening or expressive-speaking) in typically developing (TD) children aged 3 to 9 years. Five databases were searched, resulting in seven included studies. The characteristics of animated stimuli, the manner of presentation, and the language-related tasks were recorded, and questions were posed about the effect of brief animation on children's receptive and expressive language abilities. The evidence suggests that animation may have a positive effect on expressive language abilities of children compared to static pictures. As far as the effect of animation on receptive language performance is concerned, the evidence is less concrete. Future directions regarding the potential of animation on language development are discussed.

Monocyte Chemoattractant Protein-1 (MCP-1), Activin-A and Clusterin in Children and Adolescents with Obesity or Type-1 Diabetes Mellitus.

Inflammation plays a crucial role in diabetes and obesity through macrophage activation. Macrophage chemoattractant protein-1 (MCP-1), activin-A, and clusterin are chemokines with known roles in diabetes and obesity. The aim of this study is to investigate their possible diagnostic and/or early prognostic values in children and adolescents with obesity and type-1 diabetes mellitus (T1DM). METHODS: We obtained serum samples from children and adolescents with a history of T1DM or obesity, in order to measure and compare MCP-1, activin-A, and clusterin concentrations. RESULTS: Forty-three subjects were included in each of the three groups (controls, T1DM, and obesity). MCP-1 values were positively correlated to BMI z-score. Activin-A was increased in children with obesity compared to the control group. A trend for higher values was detected in children with T1DM. MCP-1 and activin-A levels were positively correlated. Clusterin levels showed a trend towards lower values in children with T1DM or obesity compared to the control group and were negatively correlated to renal function. CONCLUSIONS: The inflammation markers MCP-1, activin-A, and clusterin are not altered in children with T1DM. Conversely, obesity in children is positively correlated to serum MCP-1 values and characterized by higher activin-A levels, which may reflect an already established systematic inflammation with obesity since childhood.

"When," "Where," and "How" of SARS-CoV-2 Infection Affects the Human Cardiovascular System: A Narrative Review.

Coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory coronavirus-2 (SARS-CoV-2). Several explanations for the development of cardiovascular complications during and after acute COVID-19 infection have been hypothesized. The COVID-19 pandemic, caused by SARS-CoV-2, has emerged as one of the deadliest pandemics in modern history. The myocardial injury in COVID-19 patients has been associated with coronary spasm, microthrombi formation, plaque rupture, hypoxic injury, or cytokine storm, which have the same pathophysiology as the three clinical variants of Kounis syndrome. The angiotensin-converting enzyme 2 (ACE2), reninaldosterone system (RAAS), and kinin-kallikrein system are the main proposed mechanisms contributing to cardiovascular complications with the COVID-19 infection. ACE receptors can be found in the heart, blood vessels, endothelium, lungs, intestines, testes, neurons, and other human body parts. SARS-CoV-2 directly invades the endothelial cells with ACE2 receptors and constitutes the main pathway through which the virus enters the endothelial cells. This causes angiotensin II accumulation downregulation of the ACE2 receptors, resulting in prothrombotic effects, such as hemostatic imbalance via activation of the coagulation cascade, impaired fibrinolysis, thrombin generation, vasoconstriction, endothelial and platelet activation, and pro-inflammatory cytokine release. The KKS system typically causes vasodilation and regulates tissue repair, inflammation, cell proliferation, and platelet aggregation, but SARS-CoV-2 infection impairs such counterbalancing effects. This cascade results in cardiac arrhythmias, cardiac arrest, cardiomyopathy, cytokine storm, heart failure, ischemic myocardial injuries, microvascular disease, Kounis syndrome, prolonged COVID, myocardial fibrosis, myocarditis, new-onset hypertension, pericarditis, postural orthostatic tachycardia syndrome, pulmonary hypertension, stroke, Takotsubo syndrome, venous thromboembolism, and thrombocytopenia. In this narrative review, we describe and elucidate when, where, and how COVID-19 affects the human cardiovascular system in various parts of the human body that are vulnerable in every patient category, including children and athletes.

A Greek Pediatric Word Recognition Test by Picture Identification.

(1) Background: The study aimed to construct a clinically valuable closet-set WRS test with a picture identification task for young Greek-speaking children. (2) Methods: The test material was meticulously designed based on specific criteria. To determine which parts of speech are used more frequently by preschool children, a spontaneous speech sample (250 words per child) was acquired from three hundred children aged 3 to 6 years (M = 4.56, SD = 0.90). The study involved the development and application of two phonemically balanced 50-word lists suitable for young children, as well as the creation of picture representations for each response set. All testing was accomplished in an audiometric booth that exceeded the audiometric rooms' ambient noise level standards. The speech signal was routed from a laptop computer to a GSI 61 audiometer, and all test items were delivered from the audiometer to the subject. (3) Results: The results indicated that materials for a WRS test for young children are developed with high face validity and are applicable for children as young as three years old. The test satisfies the essential components needed for a WRS test. It consists of two phonemically balanced 50-word lists with low-redundancy bisyllabic words, with each list containing 227 phonemes. (5) Conclusions: This novel closed-set WRS test presents a valuable tool for assessing speech perception skills in young Greek-speaking children. The test results have various applications, including diagnosis, research, and (re)habilitation.

Psychometric Properties of the Greek Version of the Autism Parenting Stress Index (APSI) among Parents of Children with Autism Spectrum Disorder.

(1) Background: This study aimed to validate the Greek version of the Autism Parenting Stress Index (APSI) among parents of children with ASD. (2) Methods: The translated version was administered to 113 parents (Male: 12, Female: 101, 39.24 years old, SD 6.70, age range, 25-58) of children diagnosed with ASD and 127 parents (Male: 24, Female: 103, 41.08 years old, SD 6.22, age range: 27-56) of typically developing children. (3) Results: Significant differences between the APSI total scores and three domains between groups were observed. Although the initial factor structure could not be replicated, the APSI's internal consistency was excellent (a = 0.914), with a high positive item-total correlation (0.900-0.917). The APSI's test-retest reliability was excellent, showing an ICC equal to 0.922 [95%, CI: 0.900-0.940]. The APSI's total score cut-off point was equal to 12.00 (AUC 0.845, p < 0.001) with a sensitivity of 0.839 and 1-specificity of 0.220. A principal component analysis of the 13 items, using varimax rotations, identified three factors, which explained approximately 45.8% of the overall variance. (4) Conclusions: The Greek version of the APSI exhibited discriminant validity for measuring parents of children with ASD. Greek health professionals can use it to assess the stress experienced by parents of children with ASD.

Effects of Transcutaneous Electrical Nervous Stimulation (TENS) on Dysphonic Patients: A Systematic Review Study.

Background and Objectives: Transcutaneous electrical nerve stimulation (TENS), a pain-alleviating and muscle-relaxing treatment used in physio-therapeutic clinical practice, has recently appeared to be just as effective in dysphonia. This review aimed at clarifying whether TENS can be an effective practice in dysphonia therapy and/or management on its own or combined with other types of interventions and, hence, whether its practice can be a useful, more widespread establishment to speech and language therapy intervention methods. Materials and Methods: A search was conducted on the PubMed database using specific terms based on the PICO search strategy. Eventually, four randomized controlled studies and four clinical trials were included. The methodological quality of the included studies was evaluated using the physiotherapy evidence-based database (PEDro) assessment tool, and this indicated high-quality research with an average score of 8.43. Results: The studies utilized various TENS devices, predominantly the Dualpex 961 device (frequency of 10 Hz, phase of 200 ms). The assessment methods varied, including auditory perception, vocal therapy, electrostimulation, audio and video perceptual assessments, and laryngeal evaluations. The clinical outcomes of TENS showed a reduction in musculoskeletal pain in various areas, while the acoustic analysis results were significant in only one study. TENS was compared to manual laryngeal therapy (LMT), placebo TENS, and vocal therapy in different studies with mixed results. Conclusions: This review supports the idea that a multidimensional approach, incorporating various therapeutic modalities (TENS, LMT, speech therapy, and vocal training) can yield positive outcomes for patients with voice disorders. Further research is needed to explore the specific mechanisms of action and optimal treatment protocols for TENS in voice therapy.

Outcomes of Atrioventricular Node Ablation and Pacing in Patients with Heart Failure and Atrial Fibrillation: From Cardiac Resynchronization Therapy to His Bundle Pacing.

Objective: To review the relevant literature on the use of atrioventricular node ablation and pacing in patients with heart failure and atrial fibrillation. Methods: APubMed/MEDLINE and SCOPUS search was performed in order to assess the clinical outcomes of atrioventricular node ablation and pacemaker implantation, as well as the complications that may occur. Results: Several clinical trials, observational analyses and meta-analyses have shown that the "pace and ablate" strategy not only improves symptoms but also can enhance cardiac performance in patients with heart failure and atrial fibrillation. Although this procedure is effective and safe, some complications may occur including worsening of heart failure, permanent fibrillation, arrhythmias and sudden death. Regarding pacemaker implantation, cardiac resynchronization therapy is shown to be the optimal choice compared to right ventricle apical pacing. His bundle pacing is a promising alternative to cardiac resynchronization therapy and has shown beneficial effects, while left bundle branch pacing is an innovative modality. Conclusions: Atrioventricular node ablation and pacemaker implantation is shown to have beneficial effects on clinical outcomes of patients with atrial fibrillation ± heart failure who do not respond or are intolerant to medical treatment. Cardiac resynchronization therapy is the treatment of choice and His bundle pacing seems to be an effective alternative way of pacing in these patients.

Speech deficits in multiple sclerosis: a narrative review of the existing literature.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating autoimmune disease. MS patients deal with motor and sensory impairments, visual disabilities, cognitive disorders, and speech and language deficits. The study aimed to record, enhance, update, and delve into our present comprehension of speech deficits observed in patients with MS and the methodology (assessment tools) studies followed. The method used was a search of the literature through the databases for May 2015 until June 2022. The reviewed studies offer insight into speech impairments most exhibited by MS patients. Patients with MS face numerous communication changes concerning the phonation system (changes observed concerning speech rate, long pause duration) and lower volume. Moreover, the articulation system was affected by the lack of muscle synchronization and inaccurate pronunciations, mainly of vowels. Finally, there are changes regarding prosody (MS patients exhibited monotonous speech). Findings indicated that MS patients experience communication changes across various domains. Based on the reviewed studies, we concluded that the speech system of MS patients is impaired to some extent, and the patients face many changes that impact their conversational ability and the production of slower and inaccurate speech. These changes can affect MS patients' quality of life.

Effects of COVID-19 Infection and Vaccination on the Female Reproductive System: A Narrative Review

Several studies and research papers have been published to elucidate and understand the mechanism of the coronavirus disease 2019 (COVID-19) pandemic and its long-term effects on the human body. COVID-19 affects a number of organs, including the female reproductive system. However, less attention has been given to the effects of COVID-19 on the female reproductive system due to their low morbidity. The results of studies investigating the relationship between COVID-19 infection and ovarian function in women of reproductive age have shown the harmless involvement of COVID-19 infection. Several studies have reported the involvement of COVID-19 infection in oocyte quality, ovarian function, and dysfunctions in the uterine endometrium and the menstrual cycle. The findings of these studies indicate that COVID-19 infection negatively affects the follicular microenvironment and dysregulate ovarian function. Although the COVID-19 pandemic and female reproductive health have been studied in humans and animals, very few studies have examined how COVID-19 affects the female reproductive system. The objective of this review is to summarize the current literature and categorize the effects of COVID-19 on the female reproductive system, including the ovaries, uterus, and hormonal profiles. The effects on oocyte maturation, oxidative stress, which causes chromosomal instability and apoptosis in ovaries, in vitro fertilization cycle, high-quality embryos, premature ovarian insufficiency, ovarian vein thrombosis, hypercoagulable state, women's menstrual cycle, the hypothalamus-pituitary-ovary axis, and sex hormones, including estrogen, progesterone, and the anti-Müllerian hormone, are discussed in particular.

Body-Size Misperception among Overweight Children and Adolescents in Greece: A Cross-Sectional Study.

Childhood obesity can affect both physical and mental health. Body-size misperception may lead to a lack of motivation to make healthy changes or to engage in unhealthy weight loss behaviors, increasing the possibility for obese children to become obese adults. To estimate the frequency of body-size misperception among children and adolescents, we conducted a cross-sectional study within another study on eating disorders in youth in Greece (National Institute of Educational Policy, act no. 04/2018). Between January and December 2019, two trained assistants visited 83 primary and secondary schools of the Region of Western Greece and interviewed 3504 children aged 10-16 years (CL 99%) and performed anthropometric measurements. Among the 3504 surveyed children, 1097 were overweight, including 424 obese, and 51 were underweight. The "perceived" BMI was not computed in 875 children (25%), who did not state their weight or height and were classified as non-responders. Weight bias was inversely related to BMI, the obese and overweight non-obese children underestimated their weight, while the underweight children overestimated it. Conversely, height bias was positively related to BMI bias. BMI bias was not related to sex, age, parental education, or place of residence. In conclusion, our study lends robust support to the existing evidence on unrealistic body images among overweight children and adolescents. Prompt recognition of such misperceptions may help in increasing motivation towards healthier eating habits, systematic physical activity, and weight-control interventions.

Novel Indices to Improve the Diagnostic Ability of Nocturnal Oximetry in Children with OSAS.

Nocturnal pulse oximetry (NOx) is an alternative diagnostic test for obstructive sleep apnea syndrome (OSAS) in childhood yet with variable diagnostic performance. Our aim was to apply advanced signal analysis to develop novel and more accurate NOx indices. We studied 45 children aged 3-10 years who underwent adenotonsillectomy for adenotonsillar hypertrophy and OSAS symptoms. Participants performed NOx before and three months after surgery, and the changes in McGill oximetry score (MOS), oxygen desaturation ≥3% index (ODI3), and the novel parameters-cumulative saturation area (CSA) and oxygen saturation sample entropy (SSE)-were assessed. There was a significant improvement (p < 0.001) in all NOx indices. When pre- and post-adenotonsillectomy NOx recordings were compared, the MOS had an area under the curve (AUC) of 0.811 with 63.2% sensitivity and 100% specificity at a cutoff >1. The AUC of ODI3 was 0.994, with 97.8% sensitivity and 91.1% specificity at a cutoff of >3.6 events per hour. The CSA and SSE had an AUC of 1.00, with 100% sensitivity and specificity at a cutoff of >293 and >0.99, respectively. We conclude that the herein-introduced indices-CSA and SSE-hold promise in improving the diagnostic ability of NOx in children suspected of OSAS.

Molecular Epidemiology of SARS-CoV-2: The Dominant Role of Arginine in Mutations and Infectivity.

Background, Aims, Methods, Results, Conclusions: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global challenge due to its ability to mutate into variants that spread more rapidly than the wild-type virus. The molecular biology of this virus has been extensively studied and computational methods applied are an example paradigm for novel antiviral drug therapies. The rapid evolution of SARS-CoV-2 in the human population is driven, in part, by mutations in the receptor-binding domain (RBD) of the spike (S-) protein, some of which enable tighter binding to angiotensin-converting enzyme (ACE2). More stable RBD-ACE2 association is coupled with accelerated hydrolysis by proteases, such as furin, trypsin, and the Transmembrane Serine Protease 2 (TMPRSS2) that augment infection rates, while inhibition of the 3-chymotrypsin-like protease (3CLpro) can prevent the viral replication. Additionally, non-RBD and non-interfacial mutations may assist the S-protein in adopting thermodynamically favorable conformations for stronger binding. This study aimed to report variant distribution of SARS-CoV-2 across European Union (EU)/European Economic Area (EEA) countries and relate mutations with the driving forces that trigger infections. Variants' distribution data for SARS-CoV-2 across EU/EEA countries were mined from the European Centre for Disease Prevention and Control (ECDC) based on the sequence or genotyping data that are deposited in the Global Science Initiative for providing genomic data (GISAID) and The European Surveillance System (TESSy) databases. Docking studies performed with AutoDock VINA revealed stabilizing interactions of putative antiviral drugs, e.g., selected anionic imidazole biphenyl tetrazoles, with the ACE2 receptor in the RBD-ACE2 complex. The driving forces of key mutations for Alpha, Beta, Gamma, Delta, Epsilon, Kappa, Lambda, and Omicron variants, which stabilize the RBD-ACE2 complex, were investigated by computational approaches. Arginine is the critical amino acid in the polybasic furin cleavage sites S1/S2 (681-PRRARS-686) S2' (814-KRS-816). Critical mutations into arginine residues that were found in the delta variant (L452R, P681R) and may be responsible for the increased transmissibility and morbidity are also present in two widely spreading omicron variants, named BA.4.6 and BQ.1, where mutation R346T in the S-protein potentially contributes to neutralization escape. Arginine binders, such as Angiotensin Receptor Blockers (ARBs), could be a class of novel drugs for treating COVID-19.

Left Atrial Deformation in Heart Failure: A Clinical Update.

Despite left ventricular global longitudinal strain is an eminent and validated marker of cardiovascular disease, assessment of left atrial size and function may have incremental role in diagnosis and management of cardiovascular disease. Left atrial strain, measured by 2-dimensional speckle tracking echocardiography, is a non-invasive biomarker for the assessment of left atrial function. This novel marker, has additional value to traditional echocardiography markers of left atrial function such as left atrial diameter and volume for the diagnosis and management of left ventricular diastolic dysfunction, heart failure with preserved ejection fraction, atrial fibrillation and valvular disease. However, there are potent limitations for its use in the daily clinical practice, regarding loading conditions, image acquisition and heart rate. The aim of this review is to summarize the published evidence about left atrial strain, as assessed by speckle tracking imaging, and to discuss its clinical implications and its potent limitations.

The Effect of Long COVID-19 Infection and Vaccination on Male Fertility; A Narrative Review.

Earlier research has suggested that the male reproductive system could be particularly vulnerable to SARS-CoV-2 (COVID-19) infection, and infections involving this novel disease not only pose serious health threats but could also cause male infertility. Data from multi-organ research during the recent outbreak indicate that male infertility might not be diagnosed as a possible consequence of COVID-19 infection. Several review papers have summarized the etiology factors on male fertility, but to date no review paper has been published defining the effect of COVID-19 infection on male fertility. Therefore, the aim of this study is to review the published scientific evidence regarding male fertility potential, the risk of infertility during the COVID-19 pandemic, and the impact of COVID-19 vaccination on the male reproductive system. The effects of COVID-19 infection and the subsequent vaccination on seminal fluid, sperm count, sperm motility, sperm morphology, sperm viability, testes and sex hormones are particularly reviewed.

Antioxidant Defense and Pseudoexfoliation Syndrome: An Updated Review.

Oxidative stress (OS) affects the anterior ocular tissues, rendering them susceptible to several eye diseases. On the other hand, protection of the eye from harmful factors is achieved by unique defense mechanisms, including enzymatic and non-enzymatic antioxidants. The imbalance between oxidants and antioxidants could be the cause of pseudoexfoliation syndrome (PEXS), a condition of defective extracellular matrix (ECM) remodeling. A systematic English-language literature review was conducted from May 2022 to June 2022. The main antioxidant enzymes protecting the eye from reactive oxygen species (ROS) are superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), which catalyze the reduction of specific types of ROS. Similarly, non-enzymatic antioxidants such as vitamins A, E and C, carotenoids and glutathione (GSH) are involved in removing ROS from the cells. PEXS is a genetic disease, however, environmental and dietary factors also influence its development. Additionally, many OS products disrupting the ECM remodeling process and modifying the antioxidative defense status could lead to PEXS. This review discusses the antioxidative defense of the eye in association with PEXS, and the intricate link between OS and PEXS. Understanding the pathways of PEXS evolution, and developing new methods to reduce OS, are crucial to control and treat this disease. However, further studies are required to elucidate the molecular pathogenesis of PEXS.

Fibroblast Growth Factor-2 (FGF-2) Expression in Pterygia Using Cell Spot Arrays.

Fibroblast growth factor (FGF) is a main regulator of cell differentiation, cell migration and angiogenesis in normal and abnormal conjunctiva epithelia, but specific mechanisms of its aberrant expression are yet to be investigated. In the present study, we investigated FGF-2 protein expression within several pterygia. Using a liquid-based cytology assay, we obtained cell specimens from pterygia and healthy tissues directly from patients. A combination of immunocytochemistry followed by digital image analysis showed significant overexpression of FGF-2 in all the examined pterygia. In 30/60 (50%) cases there were high levels of staining intensity, whereas in the remaining 30/60 (50%) cases there were moderate levels of expression. FGF-2 levels of the control group were significantly lower in comparison with the pterygia group. There was no significant correlation between FGF-2 levels and either sex or location of the pterygium. FGF-2 levels had a significant correlation with morphological characteristics of the pterygia. More specifically, FGF-2 levels were significantly higher in the pterygia with a fleshy morphology. Interestingly, recurrent lesions demonstrated high expression levels. An overexpression of FGF-2 has been observed frequently in pterygia, where it may play a crucial role in determining the lesion's progression. FGF-2 upregulation correlates with the morphology of pterygia and its tendency to recur. Cell spot analysis based on liquid-based cytology is a simple, yet effective, method for detecting a broad spectrum of protein markers and could be useful in analyzing potential pterygia patient samples.