Health Related Quality of Life and Cardiovascular Risk Factors.

Cardiovascular diseases (CVD) is associated with deteriorating of quality of life (QOL) and exercise capacity (EC) but less is known on how EC interplays with QOL. The present study explores the relationship between quality of life and cardiovascular risk factors in people who present in cardiology clinics. A total of 153 adult presentations completed the SF-36 Health Survey and provided data for hypertension, diabetes mellitus, smoking, obesity, hyperlipidemia and history of coronary heart disease. Physical capacity was assessed by treadmill test. were correlated with the scores of the psychometric questionnaires. Participants with longer duration on treadmill exercise score higher on the scale of physical functioning. The study found that treadmill exercise intensity and duration were associated with improved scores in dimensions of the physical component summary and the physical functioning of SF-36, respectively. The presence of cardiovascular risk factors is related to a decreased quality of life. Patients with cardiovascular diseases should undergo particularly detailed analysis of the quality of life along with specific mental factors such as depersonalization and posttraumatic stress disorder.

Left Axillary Access for Transcatheter Aortic Valve Implantation in a Patient With Two Dependent Internal Mammary Artery Grafts and a Permanent Left-Sided Implanted Pacemaker.

Transfemoral access has been established as the gold standard approach for the majority of patients undergoing transcatheter aortic valve implantation (TAVI). However, in cases with anatomical difficulties or severely diffused peripheral arterial disease, alternative vascular access may be considered such as the transaxillary approach. We present the case of a 92-year-old gentleman with exertional dyspnea due to severe symptomatic aortic stenosis and a history of peripheral femoro-femoral bypass surgery, coronary arterial bypass surgery and a permanent dual-chamber left-side implanted pacemaker. Due to the high surgical risk and the severe anatomical difficulties, the method of TAVI using the left axillary approach was opted. A 14-F vascular sheath was inserted with surgical cutdown and with fluoroscopic guidance while small injections of contrast confirmed the non-occlusive position and the patency of the left internal mammary artery (LIMA) graft. A stiff guidewire was used to cross the heavily calcified aortic valve and subsequently was placed into the left ventricle. Balloon aortic valvuloplasty was performed followed by a successful TAVI with no significant aortic regurgitation or paravalvular leak. The patient recuperated uneventfully and was discharged after 72 h. Axillary access for TAVI is a feasible option for high-risk patients with extended peripheral arteriopathy. To our knowledge this is the first case report describing the implantation of a newer type of intra-annular self-expanding valve platform in a nonagenarian patient with severe comorbidities and such a remarkable history of multiple previous interventions in the selected access site. Meticulous upfront strategy planning and efficient collaboration between specialties is of outmost importance in hybrid procedures for favorable clinical outcomes, especially in cases with challenging anatomies.

Understanding common key indicators of successful and unsuccessful cancer drug trials using a contrast mining framework on ClinicalTrials.gov.

Clinical trials are essential to the process of new drug development. As clinical trials involve significant investments of time and money, it is crucial for trial designers to carefully investigate trial settings prior to designing a trial. Utilizing trial documents from ClinicalTrials.gov, we aim to understand the common characteristics of successful and unsuccessful cancer drug trials to provide insights about what to learn and what to avoid. In this research, we first computationally classified cancer drug trials into successful and unsuccessful cases and then utilized natural language processing to extract eligibility criteria information from the trial documents. To provide explainable and potentially modifiable recommendations for new trial design, contrast mining was applied to discoverhighly contrasted patterns with a significant difference in prevalence between successful (completion with advancement to the next phase) and unsuccessful (suspended, withdrawn, or terminated) groups. Our method identified contrast patterns consisting of combinations of drug categories, eligibility criteria, study organization, and study design for nine major cancers. In addition to a literature review for the qualitative validation of mined contrast patterns, we found that contrast-pattern-based classifiers using the top 200 contrast patterns as feature representations can achieve approximately 80% F1 score for eight out of ten cancer types in our experiments. In summary, aligning with the modernization efforts of ClinicalTrials.gov, our study demonstrates that understanding the contrast characteristics of successful and unsuccessful cancer trials may provide insights into the decision-making process for trial investigators and therefore facilitate improved cancer drug trial design.

One-year duplex ultrasound-assessed closure outcomes of percutaneous endovenous microwave ablation for the treatment of varicose veins of the lower limbs.

PURPOSE: This study aims to investigate the safety and efficacy of a new device using microwave technology for the endovenous ablation of the great saphenous vein (GSV) causing symptomatic lower limb varicose veins (LLVV). MATERIALS AND METHODS: This prospective, single-arm, single-center, cohort study investigated the safety and effectiveness of endovenous microwave ablation for the treatment of symptomatic LLVV. Enrollment period was set between January and December 2020. Primary safety endpoint was the occurrence of procedure-related complications and primary efficacy endpoint was anatomical success defined as the duplex ultrasound (DUS)-proven GSV occlusion at 1 year follow-up. Secondary endpoints included 1-year clinical success (CEAP classification improvement), repeat procedures rate due to GSV recanalization, and pain assessment at 24 h post treatment. RESULTS: In total, 50 patients (42 female; mean age: 62 ± 12 years) with 64 limbs were treated. No procedure-related complications were noted. Technical success was 95.3% (61/64 GSVs), as three cases of GSV recanalization were detected. Clinical success was 100%, as in all cases symptoms improvement by at least one grade according to CEAP classification, was achieved. Mean CEAP grade significantly improved from 3.3 ± 0.72 (median: 3) at baseline to 1.8 ± 0.85 (median: 2) at 1-year (p < 0.0001). There were no repeat procedures due to GSC recanalization. The median 24-h VAS value was 2 (mean: 1.9 ± 1.4). CONCLUSIONS: Endovenous microwave ablation was safe and effective for the treatment of varicose veins, achieving high 1-year GSV occlusion rates.

Left Anterior Descending Artery Dissection in a Female Patient With History of Chest Radiation Treatment and Separate Ostia of the Left Coronary Arteries.

Obstructive and flow limiting coronary artery dissections can be a catastrophic clinical scenario, requiring urgent treatment and tailored approach for each case. A 55-year-old female patient, with a history of breast cancer, chest radiation treatments and hypertension presented with episodes of angina and significant area of reversible ischemia on single-photon emission computerized tomography (SPECT). Coronary angiogram revealed separate ostia of the left coronary arteries and three-vessel disease (SYNTAX (Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery) = 15); subsequent full revascularization was achieved successfully with two drug-eluting stents (DES) (mid left anterior descending artery (LAD), left circumflex coronary artery (LCx)) and one drug-coated balloon (posterior descending artery (PDA)). However, after a few hours the patient underwent an urgent second angiography due to ongoing chest pain and electrocardiogram (ECG) changes. Proximal complete occlusion of the anomalous LAD was displayed and a long dissection attributable to an intimal tear following first stent implantation was recorded (well expanded and apposed stent (proximal stent edges were implanted in an unhealthy vessel area infiltrated with fibrotic and calcified plaque) not detectable by conventional angiography). A second 3.5 × 38 mm DES was implanted optimally in the proximal LAD segment and overlapped with the first one, with immediate restoration of the flow and relief of the patient's symptoms. The patient was discharged symptom free and with recommendation for optimal medical treatment for secondary coronary artery disease (CAD) prevention. Conventional coronary angiography in patients with history of chest radiation treatment might not detect accurately the extent and characteristics of the underlying CAD. Appropriate use of intravascular imaging in these cases secures a safe approach for ambiguous lesions and facilitates treatment of iatrogenic coronary dissections following PCI.

Immune-Related Gene Signatures to Predict the Effectiveness of Chemoimmunotherapy in Triple-Negative Breast Cancer Using Exploratory Subgroup Discovery.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options. Although immunotherapy has shown potential in TNBC patients, clinical studies have only demonstrated a modest response. Therefore, the exploration of immunotherapy in combination with chemotherapy is warranted. In this project we identified immune-related gene signatures for TNBC patients that may explain differences in patients' outcomes after anti-PD-L1+chemotherapy treatment. First, we ran the exploratory subgroup discovery algorithm on the TNBC dataset comprised of 422 patients across 24 studies. Secondly, we narrowed down the search to twelve homogenous subgroups based on tumor mutational burden (TMB, low or high), relapse status (disease-free or recurred), tumor cellularity (high, low and moderate), menopausal status (pre- or post) and tumor stage (I, II and III). For each subgroup we identified a union of the top 10% of genotypic patterns. Furthermore, we employed a multinomial regression model to predict significant genotypic patterns that would be linked to partial remission after anti-PD-L1+chemotherapy treatment. Finally, we uncovered distinct immune cell populations (T-cells, B-cells, Myeloid, NK-cells) for TNBC patients with various treatment outcomes. CD4-Tn-LEF1 and CD4-CXCL13 T-cells were linked to partial remission on anti-PD-L1+chemotherapy treatment. Our informatics pipeline may help to select better responders to chemoimmunotherapy, as well as pinpoint the underlying mechanisms of drug resistance in TNBC patients at single-cell resolution.

TBX21 Methylation as a Potential Regulator of Immune Suppression in CMS1 Subtype Colorectal Cancer.

Cytotoxic T lymphocyte (CTL) infiltration is associated with survival, recurrence, and therapeutic response in colorectal cancer (CRC). Immune checkpoint inhibitor (ICI) therapy, which requires CTLs for response, does not work for most CRC patients. Therefore, it is critical to improve our understanding of immune resistance in this disease. We utilized 2391 CRC patients and 7 omics datasets, integrating clinical and genomic data to determine how DNA methylation may impact survival and CTL function in CRC. Using comprehensive molecular subtype (CMS) 1 patients as reference, we found TBX21 to be the only gene with altered expression and methylation that was associated with CTL infiltration. We found that CMS1 patients with high TBX21 expression and low methylation had a significant survival advantage. To confirm the role of Tbx21 in CTL function, we utilized scRNAseq data, demonstrating the association of TBX21 with markers of enhanced CTL function. Further analysis using pathway enrichment found that the genes TBX21, MX1, and SP140 had altered expression and methylation, suggesting that the TP53/P53 pathway may modify TBX21 methylation to upregulate TBX21 expression. Together, this suggests that targeting epigenetic modification more specifically for therapy and patient stratification may provide improved outcomes in CRC.

Asclepion of Epidaurus: the application of a historical perspective in medical education.

BACKGROUND: The Asclepion of Epidaurus is one of the first healing environments in the world. Descendants of Asclepius, specifically medical students, have been singularly deprived of any information concerning this legacy. This article illuminates the role of Asclepion of Epidaurus and examines the view of medical students upon the subject and the possible benefits of this knowledge in their medical education. METHODS: The participants were 105 senior-year students from the Athens Medical School, who attended a multi-media assisted lecture related to the structure and the role of the Asclepion of Epidaurus. Afterwards, they answered anonymously a questionnaire of 12 pairs of opposite adjectives in order to describe their view regarding the meaning of Asclepion. The method used in the evaluation of their answers was that of semantic differential. RESULTS: The attitude of the students towards the meaning of Asclepion was positive, showing interest and excitement about a powerful, though unfamiliar piece of knowledge. CONCLUSION: Today's novice doctors have welcomed the concept of Asclepion as essential knowledge for the service they will be called to fulfill. The potential benefits of the Asclepian ideals in medical education and ethos are thoroughly discussed.

Psychopathology and Alexithymia in Patients with Moderate-to-Severe Psoriasis: Development of a Novel Index with Prognostic Value.

BACKGROUND: Psoriasis is a chronic, relapsing, inflammatory disease with a high risk of developing mental health difficulties. OBJECTIVE: The purposes of the study were to evaluate in moderate-to-severe psoriasis (a) the prevalence of depression and psychopathology, (b) the relationship between depression, psychopathology symptoms, and alexithymia, including its three dimensions, difficulty in identifying feelings (DIF), difficulty in describing feelings (DDF), and externally oriented thinking (EOT), and (c) to establish a novel index for the development of depression according to patients' psychopathological profile. METHODS: In 104 patients, alexithymia was evaluated with the Toronto Alexithymia Scale (TAS-20), depression with the Beck Depression Inventory (BDI), and psychopathology with the Brief Symptom Inventory SCL-90 (SCL90). A psychopathology index that combines information from the BDI and SCL90 scales was constructed and the performance of the index with alexithymia was examined. RESULTS: Female patients and active smokers score higher on BDI and SCL90 scales. Overweight patients tend to score arithmetically higher. The psychopathology index developed correlates significantly with age, DIF, DDF, and TAS-20. DIF, DDF, and TAS-20 are significant predictors of the psychopathology index. Patients with alexithymia/possible alexithymia are six times as likely to score higher in one of the psychopathology scales. CONCLUSIONS: Alexithymia is a significant factor in the development of psychopathology in psoriasis patients. The use of the proposed novel psychopathology index could be essential in order to identify patients with moderate-to-severe psoriasis who are more likely to experience depression and psychopathology. This could have an impact on the decision-making of psoriasis treatment and monitoring of the patient.

Burnout Related to Diabetes Mellitus: A Critical Analysis.

Background: Diabetes burnout is a condition when a patient with diabetes feels tired from his/her disease and neglects it for a certain period or continuously. Objective: Diabetes burnout is frequent, and there is extended literature about psychosocial stress and its negative effects on health. Methods: A search for relevant studies was conducted using PubMed, Google Scholar and ResearchGate. A systematic review was conducted on the relevant articles after critical appraisal. Only publications in English were selected. The objective of this study was to evaluate the association between burnout syndrome and diabetes mellitus. Results: This article mainly focused on studies that evaluated the presence of burnout and diabetes mellitus effects. Diabetes can influence psychological health equally with somatic strength. Relatives can also express depression, guilt, fright, worry, rage, and burnout. Psychosocial job stress and extended working hours are linked with a higher possibility of myocardial infarction, diabetes mellitus, and hypertension. Conclusion: Diabetes burnout is a combination of emotions and practices, ranging from tiredness to indifference, linked with a distressing sense of hopelessness. Revealing this health condition is necessary so that preventive measures can be taken.

Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer.

Breast cancer (BC) is the leading cause of death among female patients with cancer. Patients with triple-negative breast cancer (TNBC) have the lowest survival rate. TNBC has substantial heterogeneity within the BC population. This study utilized our novel patient stratification and drug repositioning method to find subgroups of BC patients that share common genetic profiles and that may respond similarly to the recommended drugs. After further examination of the discovered patient subgroups, we identified five homogeneous druggable TNBC subgroups. A drug repositioning algorithm was then applied to find the drugs with a high potential for each subgroup. Most of the top drugs for these subgroups were chemotherapy used for various types of cancer, including BC. After analyzing the biological mechanisms targeted by these drugs, ferroptosis was the common cell death mechanism induced by the top drugs in the subgroups with neoplasm subdivision and race as clinical variables. In contrast, the antioxidative effect on cancer cells was the common targeted mechanism in the subgroup of patients with an age less than 50. Literature reviews were used to validate our findings, which could provide invaluable insights to streamline the drug repositioning process and could be further studied in a wet lab setting and in clinical trials.

Differences in Performance of ASD and ADHD Subjects Facing Cognitive Loads in an Innovative Reasoning Experiment.

We aim to investigate whether EEG dynamics differ in adults with ASD (Autism Spectrum Disorders) and ADHD (attention-deficit/hyperactivity disorder) compared with healthy subjects during the performance of an innovative cognitive task, Aristotle's valid and invalid syllogisms, and how these differences correlate with brain regions and behavioral data for each subject. We recorded EEGs from 14 scalp electrodes (channels) in 21 adults with ADHD, 21 with ASD, and 21 healthy, normal subjects. The subjects were exposed in a set of innovative cognitive tasks (inducing varying cognitive loads), Aristotle's two types of syllogism mentioned above. A set of 39 questions were given to participants related to valid-invalid syllogisms as well as a separate set of questionnaires, in order to collect a number of demographic and behavioral data, with the aim of detecting shared information with values of a feature extracted from EEG, the multiscale entropy (MSE), in the 14 channels ('brain regions'). MSE, a nonlinear information-theoretic measure of complexity, was computed to extract a feature that quantifies the complexity of the EEG. Behavior-Partial Least Squares Correlation, PLSC, is the method to detect the correlation between two sets of data, brain, and behavioral measures. -PLSC, a variant of PLSC, was applied to build a functional connectivity of the brain regions involved in the reasoning tasks. Graph-theoretic measures were used to quantify the complexity of the functional networks. Based on the results of the analysis described in this work, a mixed 14 × 2 × 3 ANOVA showed significant main effects of group factor and brain region* syllogism factor, as well as a significant brain region* group interaction. There are significant differences between the means of MSE (complexity) values at the 14 channels of the members of the 'pathological' groups of participants, i.e., between ASD and ADHD, while the difference in means of MSE between both ASD and ADHD and that of the control group is not significant. In conclusion, the valid-invalid type of syllogism generates significantly different complexity values, MSE, between ASD and ADHD. The complexity of activated brain regions of ASD participants increased significantly when switching from a valid to an invalid syllogism, indicating the need for more resources to 'face' the task escalating difficulty in ASD subjects. This increase is not so evident in both ADHD and control. Statistically significant differences were found also in the behavioral response of ASD and ADHD, compared with those of control subjects, based on the principal brain and behavior saliences extracted by PLSC. Specifically, two behavioral measures, the emotional state and the degree of confidence of participants in answering questions in Aristotle's valid-invalid syllogisms, and one demographic variable, age, statistically and significantly discriminate the three groups' ASD. The seed-PLC generated functional connectivity networks for ASD, ADHD, and control, were 'projected' on the regions of the Default Mode Network (DMN), the 'reference' connectivity, of which the structural changes were found significant in distinguishing the three groups. The contribution of this work lies in the examination of the relationship between brain activity and behavioral responses of healthy and 'pathological' participants in the case of cognitive reasoning of the type of Aristotle's valid and invalid syllogisms, using PLSC, a machine learning approach combined with MSE, a nonlinear method of extracting a feature based on EEGs that captures a broad spectrum of EEGs linear and nonlinear characteristics. The results seem promising in adopting this type of reasoning, in the future, after further enhancements and experimental tests, as a supplementary instrument towards examining the differences in brain activity and behavioral responses of ASD and ADHD patients. The application of the combination of these two methods, after further elaboration and testing as new and complementary to the existing ones, may be considered as a tool of analysis in helping detecting more effectively such types of disorders.

Complexity analysis of the brain activity in Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) due to cognitive loads/demands induced by Aristotle's type of syllogism/reasoning. A Power Spectral Density and multiscale entropy (MSE) analysis.

OBJECTIVE: We aim to investigate whether EEG dynamics differ in adults with ASD (Autism Spectrum Disorders), ADHD (attention-deficit/hyperactivity disorder), compared with healthy subjects during the performance of an innovative cognitive task: Aristotle's valid and invalid syllogisms. We follow the Neuroanatomical differences type of criterion in assessing the results of our study in supporting or not the dual-process theory of Kahneman, 2011) (Systems I & II of thinking). METHOD: We recorded EEGs from 14 scalp electrodes in 30 adults with ADHD, 30 with ASD and 24 healthy, normal subjects. The subjects were exposed in a set of innovative cognitive tasks (inducing varying cognitive loads), the Aristotle's four types of syllogism mentioned above. The multiscale entropy (MSE), a nonlinear information-theoretic measure or tool was computed to extract features that quantify the complexity of the EEG. RESULTS: The dynamics of the curves of the grand average of MSE values of the ADHD and ASD participants was significantly in higher levels for the majority of time scales, than the healthy subjects over a number of brain regions (electrodes locations), during the performance of both valid and invalid types of syllogism. This result is seemingly not in accordance of the broadly accepted 'theory' of complexity loss in 'pathological' subjects, but actually this is not the case as explained in the text. ADHD subjects are engaged in System II of thinking, for both Valid and Invalid syllogism, ASD and Control in System I for valid and invalid syllogism, respectively. A surprising and 'provocative' result of this paper, as shown in the next sections, is that the Complexity-variability of ASD and ADHD subjects, when they face Aristotle's types of syllogisms, is higher than that of the control subjects. An explanation is suggested as described in the text. Also, in the case of invalid type of Aristotelian syllogisms, the linguistic and visuo-spatial systems are both engaged ONLY in the temporal and occipital regions of the brain, respectively, of ADHD subjects. In the case of valid type, both above systems are engaged in the temporal and occipital regions of the brain, respectively, of both ASD and ADHD subjects, while in the control subjects only the visuo-spatial type is engaged (Goel et al., 2000; Knauff, 2007). CONCLUSION: Based on the results of the analysis described in this work, the differences in the EEG complexity between the three groups of participants lead to the conclusion that cortical information processing is changed in ASD and ADHD adults, therefore their level of cortical activation may be insufficient to meet the peculiar cognitive demand of Aristotle's reasoning. SIGNIFICANCE: The present paper suggest that MSE, is a powerful and efficient nonlinear measure in detecting neural dysfunctions in adults with ASD and ADHD characteristics, when they are called on to perform in a very demanding as well as innovative set of cognitive tasks, that can be considered as a new diagnostic 'benchmark' in helping detecting more effectively such type of disorders. A linear measure alone, as the typical PSD, is not capable in making such a distinction. The work contributes in shedding light on the neural mechanisms of syllogism/reasoning of Aristotelian type, as well as toward understanding how humans reason logically and why 'pathological' subjects deviate from the norms of formal logic.

Cardiac amyloidosis presenting with coronary artery embolization.

Amyloid light-chain (AL) amyloidosis is a multisystemic disease. Among its clinical manifestations, vein and arterial thromboembolic events are included. We report the unusual case of a 57-year-old female patient with AL amyloidosis presenting with an ST segment elevation myocardial infarction due to coronary artery embolization (CE). The patient reported a history of exertional dyspnoea along with episodes of haemoptysis for the last few months. Her coronary angiography demonstrated embolization of the distal segment of the left anterior descending artery. The main findings of her cardiac ultrasound included concentric left ventricular hypertrophy, mildly impaired left ventricular systolic function, left atrium enlargement and a restrictive-like filling pattern, while her chest computed tomography (CT) demonstrated bilateral pleural effusions. Cardiac magnetic resonance imaging that was performed afterwards, indicated areas of microvascular infarction, a small apex infarct and findings compatible with possible amyloidosis, a diagnosis that was confirmed later by fat tissue biopsy. Patient was referred for an oncology consultation, started therapy with direct oral anticoagulants, angiotensin converting enzyme inhibitor, statins and anti-plasma cell therapy. She has been improving since then and has been free of cardiovascular events for a follow-up period of 12 months. Cardiologists ought to be aware of amyloidosis as a rare but possible cause of coronary embolization, while close collaboration with oncologists is required for the establishment of the correct diagnosis.

A High-Cholesterol Diet Increases Toll-like Receptors and Other Harmful Factors in the Rabbit Myocardium: The Beneficial Effect of Statins.

BACKGROUND: A high-cholesterol diet (HCD) induces vascular atherosclerosis through vascular inflammatory and immunological processes via TLRs. The aim of this study is to investigate the mRNA expression of TLRs and other noxious biomarkers expressing inflammation, fibrosis, apoptosis, and cardiac dysfunction in the rabbit myocardium during (a) high-cholesterol diet (HCD), (b) normal diet resumption and (c) fluvastatin or rosuvastatin treatment. METHODS: Forty-eight male rabbits were randomly divided into eight groups (n = 6/group). In the first experiment, three groups were fed with HCD for 1, 2 and 3 months. In the second experiment, three groups were fed with HCD for 3 months, followed by normal chow for 1 month and administration of fluvastatin or rosuvastatin for 1 month. Control groups were fed with normal chow for 90 and 120 days. The whole myocardium was removed; total RNA was isolated from acquired samples, and polymerase chain reaction, reverse transcription PCR and quantitative real-time PCR were performed. RESULTS: mRNA of TLRs 2, 3, 4 and 8; interleukin-6; TNF-a; metalloproteinase-2; tissue inhibitor of metalloproteinase-1; tumor protein 53; cysteinyl aspartate specific proteinase-3; and brain natriuretic peptide (BNP) increased in HCD. Statins but not resumption of a normal diet decreased levels of these biomarkers and increased levels of antifibrotic factors. CONCLUSIONS: HCD increases the levels of TLRs; inflammatory, fibrotic and apoptotic factors; and BNP in the rabbit myocardium. Atherogenic diets adversely affect the myocardium at a molecular level and are reversed by statins.

Resilience of the Hellenic navy seals assessed by heart rate variability during cognitive tasks.

OBJECTIVES: The interaction between high physical performance under extreme conditions in military and the simultaneous control of the cognitive executive functioning has been a subject of research in literature for the past few decades. Stroop test and Heart-rate variability (HRV), have been verified valuable clinical tools for the assessment of cerebral and autonomic/ cardiovascular stress responses respectively. METHODS: Thirty-four subjects were enrolled in this study. Of them, 18 were candidates under intense preparation for their enlistment in the Hellenic Navy SEALs (HN-SEALs) and 16 were healthy controls (HC). All subjects underwent stroop tasks, along with mental state and personality examination. HRV variables in time and frequency domains recordings were acquired, during each aforementioned cognitive testing procedure. RESULTS: Our results showed that HNS's performance on both cognitive and emotion stroop tasks were equivalent to controls (p≥.054); however, HNS exhibited statistically significant lower levels of HRV in different time and frequency domain variables, compared to HC (ranged from p<.01 to p<.05). Finally, in a between group comparison of the psychometric tools, HNS had significantly higher somatization, anxiety and neuroticism than HC. CONCLUSION: In conclusion, these findings indicate that HNS display flexibility in their autonomic regulation during cognitive and emotional tasks. This characteristic is closely related to problem solving or adaptability skills. Therefore, we support that HRV measurement turns out to be an invaluable tool for both scientific and clinical insights, promising to be an index regarding the psychophysiological resilience especially in the neurovisceral integration (NVI) model.

Explainable artificial intelligence in high-throughput drug repositioning for subgroup stratifications with interventionable potential.

Enabling precision medicine requires developing robust patient stratification methods as well as drugs tailored to homogeneous subgroups of patients from a heterogeneous population. Developing de novo drugs is expensive and time consuming with an ultimately low FDA approval rate. These limitations make developing new drugs for a small portion of a disease population unfeasible. Therefore, drug repositioning is an essential alternative for developing new drugs for a disease subpopulation. This shows the importance of developing data-driven approaches that find druggable homogeneous subgroups within the disease population and reposition the drugs for these subgroups. In this study, we developed an explainable AI approach for patient stratification and drug repositioning. Contrast pattern mining and network analysis were used to discover homogeneous subgroups within a disease population. For each subgroup, a biomedical network analysis was done to find the drugs that are most relevant to a given subgroup of patients. The set of candidate drugs for each subgroup was ranked using an aggregated drug score assigned to each drug. The proposed method represents a human-in-the-loop framework, where medical experts use the data-driven results to generate hypotheses and obtain insights into potential therapeutic candidates for patients who belong to a subgroup. Colorectal cancer (CRC) was used as a case study. Patients' phenotypic and genotypic data was utilized with a heterogeneous knowledge base because it gives a multi-view perspective for finding new indications for drugs outside of their original use. Our analysis of the top candidate drugs for the subgroups identified by medical experts showed that most of these drugs are cancer-related, and most of them have the potential to be a CRC regimen based on studies in the literature.

Assessment of Resilience of the Hellenic Navy Seals by Electrodermal Activity during Cognitive Tasks.

Stress resilience plays a key role in task performance during emergencies, especially in occupations like military special forces, with a routine consisting of unexpected events. Nevertheless, reliable and applicable measurements of resilience in predicting task performance in stressful conditions are still researched. This study aimed to explore the stress response in the Hellenic Navy SEALs (HN-SEALs), using a cognitive-physiological approach. Eighteen candidates under intense preparation for their enlistment in the HN-SEALs and 16 healthy controls (HCs) underwent Stroop tests, along with mental-state and personality examination. Simultaneously, electrodermal activity (EDA) was assessed during each one of cognitive testing procedures. Compared to healthy control values, multiple components of EDA values were found decreased (p < 0.05) in the HN-SEALs group. These results were associated with an increase in resilience level in the HN-SEALs group, since a restricted sympathetic reactivity according to the reduced EDA values was observed during the stressful cognitive testing. This is the first report providing physiological measurements of the sympathetic response of HN-SEALs to a stressful situation and suggests that EDA turns out to be a simple and objective tool of sympathetic activation and it may be used as a complementary index of resilience in HN-SEALs candidates.

Cardiovascular toxicity of breast cancer treatment: an update.

Novel chemotherapeutic agents have marked a new era in oncology during the past decade, prolonging significantly the overall survival of breast cancer patients. Nevertheless, contemporary antineoplastic treatments can frequently cause adverse cardiovascular side effects. Common manifestations of chemotherapy-induced cardiotoxicity include cardiomyopathy, ischemia, conduction disturbances, hypertension and thromboembolic events, while the type of the treatment regimen administered crucially determines clinical outcome. The aim of this literature review is to analyze the incidence and the underlying mechanisms of cardiovascular toxicity caused by agents approved for breast cancer, as well as to describe ways of monitoring and treating the cardiotoxic effects in breast cancer patients. Moreover, our work intends to provide an easy-to-grasp synopsis of recent and clinically meaningful advances in the field.

Vascular Inflammation and Cardiovascular Burden in Metastatic Breast Cancer Female Patients Receiving Hormonal Treatment and CDK 4/6 Inhibitors or Everolimus.

Background: Chemotherapy regimens for breast cancer treatment can promote vascular dysfunction and lead to high cardiovascular risk. Purpose: To investigate the cardiovascular burden and vascular inflammation in metastatic breast cancer patients receiving CDK 4/6 inhibitors or everolimus in addition to standard hormonal treatment. Methods: 22 consecutive female patients with metastatic breast cancer were enrolled. Relative wall thickness (RWT) and left ventricle mass (LVM) measurements by transthoracic echocardiography were obtained followed by 24-h ambulatory blood pressure monitoring, and 18F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging. Uptake of the radiotracer in the aortic wall was estimated as tissue-to-background ratio (TBR). Each patient was assessed for the aforementioned parameters before the initiation and after 6 months of treatment. Results: At follow up, patients assigned to CDK 4/6 treatment demonstrated increased 24-h systolic blood pressure (SBP) (p = 0.004), daytime SBP (p = 0.004) and night time SBP (p = 0.012) (Group effect). The 24-h mean arterial pressure measurements were also higher in CDK 4/6 population, in comparison to everolimus that displayed firm values (Group effect- p = 0.035, Interaction effect-p = 0.023). Additionally, 24 h diastolic blood pressure recordings in CDK 4/6 therapy were higher opposed to everolimus that remained consistent (Interaction effect- p = 0.010). In CDK 4/6 group, TBR aorta also increased significantly, whereas TBR values in everolimus remained stable (Interaction effect-p = 0.049). Both therapeutic regimens displayed statistically significant damaging effect to RWT and LVM. Conclusion: CDK 4/6 inhibitors and hormonal treatment can lead to increased vascular inflammation, and higher blood pressure compared to the combination of everolimus and hormonal treatment. Moreover, both treatment strategies promoted left ventricle remodeling.