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    Pivotal Role of mTOR in Non-Skin Manifestations of Psoriasis
    (2024)
    Ka Joo
    ;
    Claudio Karsulovic
    ;
    Milisa Sore
    ;
    HOJMAN CANO, LIA PAULA  
    <jats:p>Psoriasis is a chronic inflammatory condition affecting 2% of the Western population. It includes diverse manifestations influenced by genetic predisposition, environmental factors, and immune status. The sustained activation of mTOR is a key element in psoriasis pathogenesis, leading to an uncontrolled proliferation of cytokines. Furthermore, mTOR activation has been linked with the transition from psoriasis to non-skin manifestations such as psoriatic arthritis and cardiovascular events. While therapies targeting pro-inflammatory cytokines have shown efficacy, additional pathways may offer therapeutic potential. The PI3K/Akt/mTOR pathway, known for its role in cell growth, proliferation, and metabolism, has emerged as a potential therapeutic target in psoriasis. This review explores the relevance of mTOR in psoriasis pathophysiology, focusing on its involvement in cutaneous and atheromatous plaque proliferation, psoriatic arthritis, and cardiovascular disease. The activation of mTOR promotes keratinocyte and synovial cell proliferation, contributing to plaque formation and joint inflammation. Moreover, mTOR activation may exacerbate the cardiovascular risk by promoting pro-inflammatory cytokine production and dysregulation lipid and glucose metabolism. The inhibition of mTOR has shown promise in preclinical studies, reducing skin inflammation and plaque proliferation. Furthermore, mTOR inhibition may mitigate cardiovascular risk by modulating cholesterol metabolism and attenuating atherosclerosis progression. Understanding the role of mTOR in psoriasis, psoriatic arthritis, and cardiovascular disease provides insight into the potential treatment avenues and sheds light on the complex interplay of the immune and metabolic pathways in these conditions.</jats:p>
    Scopus© Citations 11  7
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    Usability and feasibility of PreventS-MD web app for stroke prevention
    (2023)
    Valery L Feigin
    ;
    Rita Krishnamurthi
    ;
    Oleg Medvedev
    ;
    Alexander Merkin
    ;
    Balakrishnan Nair
    <jats:sec><jats:title>Background:</jats:title><jats:p> Most strokes and cardiovascular diseases (CVDs) are potentially preventable if their risk factors are identified and well controlled. Digital platforms, such as the PreventS-MD web app (PreventS-MD) may aid health care professionals (HCPs) in assessing and managing risk factors and promoting lifestyle changes for their patients. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> This is a mixed-methods cross-sectional two-phase survey using a largely positivist (quantitative and qualitative) framework. During Phase 1, a prototype of PreventS-MD was tested internationally by 59 of 69 consenting HCPs of different backgrounds, age, sex, working experience, and specialties using hypothetical data. Collected comments/suggestions from the study HCPs in Phase 1 were reviewed and implemented. In Phase 2, a near-final version of PreventS-MD was developed and tested by 58 of 72 consenting HCPs using both hypothetical and real patient (n = 10) data. Qualitative semi-structured interviews with real patients (n = 10) were conducted, and 1 month adherence to the preventive recommendations was assessed by self-reporting. The four System Usability Scale (SUS) groups of scores (0–50 unacceptable; 51–68 poor; 68–80.3 good; &gt;80.3 excellent) were used to determine usability of PreventS-MD. </jats:p></jats:sec><jats:sec><jats:title>Findings:</jats:title><jats:p> Ninety-nine HCPs from 27 countries (45% from low- to middle-income countries) participated in the study, and out of them, 10 HCPs were involved in the development of PreventS before the study, and therefore were not involved in the survey. Of the remaining 89 HCPs, 69 consented to the first phase of the survey, and 59 of them completed the first phase of the survey (response rate 86%), and 58 completed the second phase of the survey (response rate 84%). The SUS scores supported good usability of the prototype (mean score = 80.2; 95% CI [77.0–84.0]) and excellent usability of the final version of PreventS-MD (mean score = 81.7; 95% CI [79.1–84.3]) in the field. Scores were not affected by the age, sex, working experience, or specialty of the HCPs. One-month follow-up of the patients confirmed the high level of satisfaction/acceptability of PreventS-MD and (100%) adherence to the recommendations. </jats:p></jats:sec><jats:sec><jats:title>Interpretation:</jats:title><jats:p> The PreventS-MD web app has a high level of usability, feasibility, and satisfaction by HCPs and individuals at risk of stroke/CVD. Individuals at risk of stroke/CVD demonstrated a high level of confidence and motivation in following and adhering to preventive recommendations generated by PreventS-MD. </jats:p></jats:sec>
    Scopus© Citations 9  2
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    Scopus© Citations 21  1
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    Scopus© Citations 2  3
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    Cardiac abnormalities determined by tissue Doppler imaging and arrhythmias in adolescents with anorexia nervosa
    (2021)
    Vicente Nehgme
    ;
    Patricia Rios
    ;
    Valeria Acevedo
    ;
    Patricia Alvarez
    <jats:title>Abstract</jats:title><jats:sec id="S1047951121001852_as1"><jats:title>Background:</jats:title><jats:p>Anorexia nervosa has a prevalence of 0.5–3% in adolescents, placing this population at increased risk of cardiac anomalies including arrhythmias, pericardial effusion, and myocardial dysfunction. Our objective is to describe cardiovascular anomalies observed by tissue Doppler imaging in patients with anorexia nervosa.</jats:p></jats:sec><jats:sec id="S1047951121001852_as2"><jats:title>Methods:</jats:title><jats:p>We retrospectively reviewed electrocardiogram, Holter, and echocardiography findings in 28 patients diagnosed with anorexia nervosa.</jats:p></jats:sec><jats:sec id="S1047951121001852_as3"><jats:title>Results:</jats:title><jats:p>Electrocardiogram was abnormal in 71% of patients with sinus bradycardia observed in 57%. Holter confirmed sinus bradycardia without significant pauses. Prolonged QTc, low voltage, and ectopic beats were each seen in 14% of patients. Wenckebach atrioventricular block was observed in one patient. Supraventricular or ventricular tachycardia was not observed. Echocardiography showed structurally normal heart in all patients. Pericardial effusion was seen in 7.1% of patients and left ventricular mass was decreased in 10.7%. Mean ejection fraction was 0.73 and mean fractional shortening was 38.4%. Tissue Doppler imaging revealed systolic or diastolic dysfunction in four patients with e’, a’, and s’ velocities in the lateral and septal basal segments more than two standard deviations below the mean. Two patients had decreased left ventricular mass but no significant difference in disease duration from the group. Basal segment velocities below one standard deviation were also observed in an additional seven patients.</jats:p></jats:sec><jats:sec id="S1047951121001852_as4"><jats:title>Conclusion:</jats:title><jats:p>A trend for decreased tissue Doppler imaging velocities was seen in 25.0% of patients, while significant systolic and diastolic dysfunction was seen in 14.3% of patients, associated with a significant reduction in left ventricular mass and independent of disease duration.</jats:p></jats:sec>
    Scopus© Citations 4  1
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    New Markers for Cardiovascular Disease in Psoriatic Patients: Preliminary Study on Monocyte Phenotype, ADAMTS7, and mTOR Activity
    (2023)
    Khanty Loyola
    ;
    Claudio Karsulovic
    ;
    CABRERA MORAGA, RAUL ALEJANDRO  
    ;
    Claudio Perez
    ;
    HOJMAN CANO, LIA PAULA  
    <jats:p>Psoriasis is a skin disease with occasional involvement of non-cutaneous territories. Beyond the usual, cardiovascular events are more frequent in these patients and correlate only partially with disease activity, suggesting the presence of other unknown factors. We selected ten psoriatic patients without treatment in the last year and matched them for age and gender with eleven healthy subjects. Ficoll-extracted mononuclear cells were analyzed with flow cytometry for monocyte surface phenotype markers, intracellular NFκB/inflammasome-dependent interleukins, and chemotaxis receptor CXCR3. Using ELISA, patient serum was evaluated for ADAMTS7 and CXCL10. Inflammatory M1 monocytes showed higher levels of IL-1β and IL-6 in psoriatic patients. M2 monocytes also showed higher levels of intracellular inflammatory cytokines. Nevertheless, IL-6 values were higher compared to other monocytes and IL-1β. The mTORC activation markers ADAMTS7 and S6Rp were higher in psoriatic patients than in healthy controls. In psoriatic patients, serum levels of ADAMTS7 were elevated, and M2 monocytes showed a distinct inflammatory response with higher relative levels of NFκB-dependent IL-6 and less activity of the CXCR3–CXCL10 chemotactic pathway. These data suggest pathways with potential markers for prediction and early detection of cardiovascular risk in psoriatic patients.</jats:p>
      41Scopus© Citations 5
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    The impacts of social determinants of health and cardiometabolic factors on cognitive and functional aging in Colombian underserved populations
    (2023)
    Hernando Santamaria-Garcia
    ;
    Sebastian Moguilner
    ;
    Odir Antonio Rodriguez-Villagra
    ;
    Felipe Botero-Rodriguez
    ;
    Stefanie Danielle Pina-Escudero
    <jats:title>Abstract</jats:title><jats:p>Global initiatives call for further understanding of the impact of inequity on aging across underserved populations. Previous research in low- and middle-income countries (LMICs) presents limitations in assessing combined sources of inequity and outcomes (i.e., cognition and functionality). In this study, we assessed how social determinants of health (SDH), cardiometabolic factors (CMFs), and other medical/social factors predict cognition and functionality in an aging Colombian population. We ran a cross-sectional study that combined theory- (structural equation models) and data-driven (machine learning) approaches in a population-based study (<jats:italic>N</jats:italic> = 23,694;<jats:italic>M</jats:italic> = 69.8 years) to assess the best predictors of cognition and functionality. We found that a combination of SDH and CMF accurately predicted cognition and functionality, although SDH was the stronger predictor. Cognition was predicted with the highest accuracy by SDH, followed by demographics, CMF, and other factors. A combination of SDH, age, CMF, and additional physical/psychological factors were the best predictors of functional status. Results highlight the role of inequity in predicting brain health and advancing solutions to reduce the cognitive and functional decline in LMICs.</jats:p>
    Scopus© Citations 10  1
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      6Scopus© Citations 114
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    Updated clinical practice recommendations for managing children with 22q11.2 deletion syndrome
    (2023)
    Sólveig Óskarsdóttir
    ;
    Erik Boot
    ;
    Terrence Blaine Crowley
    ;
    Joanne C.Y. Loo
    ;
    Jill M. Arganbright
    Scopus© Citations 50  2
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    Ultrasound-guided femoral access in patients with vascular closure devices: a prespecified analysis of the randomised UNIVERSAL trial
    (2023)
    Marc-André d'Entremont
    ;
    Sulaiman Alrashidi
    ;
    Omar Alansari
    ;
    Bradley Brochu
    ;
    Laura Heenan
      1Scopus© Citations 19