Nanoscale Technologies for Prevention and Treatment of Heart Failure: Challenges and Opportunities.

The adult myocardium has a limited regenerative capacity following heart injury, and the lost cells are primarily replaced by fibrotic scar tissue. Suboptimal efficiency of current clinical therapies to resurrect the infarcted heart results in injured heart enlargement and remodeling to maintain its physiological functions. These remodeling processes ultimately leads to ischemic cardiomyopathy and heart failure (HF). Recent therapeutic approaches (e.g., regenerative and nanomedicine) have shown promise to prevent HF postmyocardial infarction in animal models. However, these preclinical, clinical, and technological advancements have yet to yield substantial enhancements in the survival rate and quality of life of patients with severe ischemic injuries. This could be attributed largely to the considerable gap in knowledge between clinicians and nanobioengineers. Development of highly effective cardiac regenerative therapies requires connecting and coordinating multiple fields, including cardiology, cellular and molecular biology, biochemistry and chemistry, and mechanical and materials sciences, among others. This review is particularly intended to bridge the knowledge gap between cardiologists and regenerative nanomedicine experts. Establishing this multidisciplinary knowledge base may help pave the way for developing novel, safer, and more effective approaches that will enable the medical community to reduce morbidity and mortality in HF patients.

Mitral valve resistance determines hemodynamic consequences of severe rheumatic mitral stenosis and immediate outcomes of percutaneous valvuloplasty.

INTRODUCTION: The mitral valve area (MVA) poorly reflects the hemodynamic status of (MS). In this study, we compared the MVA with mitral valve resistance (MVR) with regard to the determination of hemodynamic consequences of MS and the immediate outcomes of percutaneous balloon mitral valvuloplasty (PBMV). METHODS: In a prospective study, 36 patients with severe rheumatic MS with left ventricular ejection fraction (LVEF) >50% were evaluated. They underwent transthoracic echocardiography (TTE) and catheterization. The MVA was measured by two-dimensional planimetry and pressure half-time (PHT), and the MVR was calculated using the equation: 1333 × transmitral pressure gradient mean transmitral diastolic flow rate. RESULTS: The patients' mean age was 47.8±10.5 years. MVR ≥140.6 dynes·s/cm5 detected systolic pulmonary arterial pressure (sPAP) >55 mm Hg with a sensitivity of 100% and a specificity of 74%. The sensitivity and specificity of MVA<0.75 cm2 to discriminate elevated sPAP were 81% and 89%, respectively. PHT ≥323.5 mseconds had a sensitivity of 78% and a specificity of 96% to detect an elevated sPAP. To predict a successful PBMV, preprocedural MVR ≥106.1 dynes·s/cm5 had a sensitivity of 100% and a specificity of 67% (area under the curve [AUC]=0.763; 95% confidence interval [CI]=0.520-1.006; P=.034); preprocedural MVA <0.95 cm2 had a sensitivity of 78% and a specificity of 73% (AUC=0.730; 95% CI=0.503-0.956; P=.065); and preprocedural PHT ≥210.5 mseconds had a sensitivity of 73% and a specificity of 78% (AUC=0.707; 95% CI=0.474-0.941; P=.095). CONCLUSIONS: MVR seems to be more accurate than MVA in determining the hemodynamic consequences of severe MS as determined by sPAP. In addition, preprocedural MVR detected successful PBMVs.

The Road Less Traveled: The Marham National Health Institute's Journey on Cleft Lip and Palate Surgery Missions.

Congenital cleft lip and palate represent the prevailing craniofacial birth anomalies on a global scale. Notably, a substantial proportion of patients within remote regions of Iran defer corrective surgery until later stages of life, often in childhood or adulthood, primarily due to intricate financial and cultural constraints. In response to this pressing healthcare challenge, a dedicated collective of volunteer plastic surgeons was established in 2009 with the explicit aim of providing medical care to these underserved patients. Over the subsequent years, this compassionate team embarked on 31 meticulously planned missions to underprivileged areas scattered across the country. Through these organized endeavors, a remarkable total of 20,579 medical visits were conducted, coupled with the performance of 2,303 essential surgeries, thus offering a lifeline of healthcare to these disadvantaged individuals.

Cardiovascular Toxicity Associated With Immune Checkpoint Inhibitor Therapy: A Comprehensive Review.

Immune checkpoint inhibitors (ICIs), a significant breakthrough treatment of cancer, exert their function through enhancing the immune system's ability to recognize and attack cancer cells. However, these revolutionary cancer treatments have been associated with a range of immune-related adverse effects, including cardiovascular toxicity. The most commonly reported cardiovascular toxicities associated with ICIs are myocarditis, pericarditis, arrhythmias, and vasculitis. These cardiovascular manifestations are often severe and can lead to life-threatening complications. Therefore, prompt identification and management of these toxicities is critical, and a multidisciplinary teamwork by cardiologists and oncologists are required to ensure optimal patient outcomes. In this review, we summarize the current knowledge on the mechanisms underlying ICI-associated cardiovascular toxicity, clinical presentations of these toxicities, potential risk factors, diagnosis, management, and surveillance strategies during ICI therapy. While ICIs have already transformed cancer treatment, further research is needed to better understand and manage their immune-related cardiovascular effects, and possibly, to identify biomarkers which can predict the occurrence of these cardiovascular complications.

A rare cause of complete heart block in an adult: Primary cardiac lymphoma.

Primary cardiac lymphoma (PCL) is a rare primary cardiac neoplasm with a relatively poor prognosis despite confinement to the heart and/or pericardium. We report a 54-year-old man who had presented with complete heart block for which he had undergone permanent pacemaker implantation, and six months later he was referred to us for evaluation of progressive exertional dyspnea. Multislice spiral computed tomography angiography of the heart and major vasculature showed infiltrative tumoral lesion that has involved interatrial septum, right atrium, left atrium, and left ventricle with invasion into the pulmonary artery. Tissue samples were taken using uniportal video-assisted thoracoscopic surgery, and the histologic examination revealed diffuse large B-cell lymphoma. Chemoimmunotherapy was effective in inducing tumor regression and the patient was still in remission during the next six months after treatment.

Heart failure with preserved ejection fraction in coronavirus disease 2019 patients: the promising role of diuretic therapy in critically ill patients.

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on diastolic function is less known. We describe a 46-year-old man with a history of mild hypertension who presented to the emergency department with fever, cough, and myalgia for 2 days. The patient was tested positive for SARS-CoV-2. He was admitted and started on a combination of antiviral and antimicrobial therapy. He developed respiratory distress 2 days later, and O2 saturation declined. Blood tests showed an increased N-terminal pro-B type natriuretic peptide (NT-proBNP) level, and echocardiography showed normal left ventricular ejection fraction and E/e' ratio of 16. Computed tomography scan showed interstitial pulmonary oedema and prominent peripheral pulmonary vascular markings. Given these findings, heart failure with preserved ejection fraction (HFpEF) was considered. Low-dose diuretic was started, and fluid administration was restricted, resulting in a decrease in NT-proBNP level, clinical and haemodynamic stabilization, and improved oxygenation. This case highlights the occurrence of HFpEF in coronavirus disease 2019.

How Left Ventricular Size Affects Severity of Disease and Long-term Prognosis in Patients with Severe Systolic Dysfunction?

BACKGROUND: We compared the severity of disease, heart failure (HF) rehospitalization and trend of changes over a 12-month follow-up in clinical and biochemical measurements between dilated cardiomyopathy (DCM) patients and those with left ventricular systolic dysfunction with normal LV size (NLVS). The existing definition of DCM failed to justify our observations in some clinical circumstances resulting in diagnostic and prognostic challenges. METHODS: A total of 77 patients [52 (67.5%) male] including 40 patients in the NLVS group and 37 patients in the DCM group were enrolled and followed up for a median of 12 months [interquartile range, 11-14 months]. RESULTS: Mean left ventricular ejection fraction was statistically comparable between NLVS and DCM patients (22 ± 8% vs. 19 ± 6%, P = 0.08]. The New York Heart Association class was statistically comparable in both groups (P = 0.23). Laboratory measurements including hemoglobin, sodium, creatinine, uric acid, and NT-proBNP level were also statistically similar in both groups (all P > 0.05). During follow-up, HF rehospitalization occurred in 16 (76%) patients in NLVS and 5 (24%) patients in DCM groups (P = 0.009). Except for left ventricular ejection fraction which improved in both NLVS and DCM groups, no significant changes were observed in clinical (New York Heart Association class) and laboratory measurements during follow-up in both NLVS and DCM groups. CONCLUSIONS: Our study showed that NLVS defines a group of systolic HF patients which not only did not have less severe disease than those with enlarged left ventricules (i.e., DCM), also had more HF rehospitalization. These NLVS patients also had steady clinical, laboratory, and echocardiographic profile during follow-up.

Spontaneous coronary artery dissection managed with a conservative or revascularization approach: a meta-analysis.

BACKGROUND: The optimal treatment approach for spontaneous coronary artery dissection (SCAD) remains unclear. OBJECTIVES: The study aims to compare in-hospital and long-term clinical outcomes of SCAD patients initially managed with medical therapy (conservative approach) versus percutaneous coronary intervention or coronary artery bypass grafting (revascularization approach) based on published data. METHODS: We identified relevant studies by performing a systematic search in the Ovid MEDLINE and Embase databases. Studies with N at least 10 that report in-hospital outcomes [death, myocardial infarction (MI) and revascularization] or long-term outcomes (death, MI, revascularization, SCAD recurrence, and heart failure) were included. Risk difference between conservative and revascularization approach was estimated with the inverse variance-weighted method in a fixed-effect or random-effect model. RESULTS: A total of 22 nonrandomized, observational studies were analyzed (N = 1435). Compared with the initial revascularization approach, the conservative approach was associated with a comparable risk of in-hospital outcomes [risk difference: death, -0.61% (95% confidence interval, -2.13-0.91%), P = 0.43; MI, -0.99% (-4.65-2.67%), P = 0.60; revascularization, -3.02% (-8.79-2.75%), P = 0.31] and long-term outcomes [death, -0.06% (-2.33-2.20%), P = 0.96; MI, 0.96% (-2.35-4.27%), P = 0.57; revascularization, -3.31% (-7.63-1.02%), P = 0.13; SCAD recurrence, 3.75% (-2.05-9.55%), P = 0.21; heart failure, -0.01% (-3.13-3.11%), P = 0.99]. There was no significant heterogeneity across these studies. CONCLUSION: Pooled results suggest that SCAD patients initially managed with a conservative strategy may have similar in-hospital and long-term outcomes compared with those who received revascularization in the absence of ongoing ischemia or left main artery involvement. More data from prospective studies are warranted to validate these findings.

Smartwatch for the Detection of Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia and poses a substantial economic burden due to associated thromboembolic complications. Screening for AF may theoretically be effective, but there is no consensus regarding the optimal screening method because the available tools are either invasive or not cost-effective. Recently, smartwatch industry has received a surge of interest for this purpose by introducing technologies such as photoplethysmography, artificial intelligence, and actual electrodes taking an electrocardiogram to measure and analyze heart rate and rhythm with relatively acceptable accuracy. Combined with other features such as ease of use and connectivity, smartwatches can potentially be used for large-scale AF screening and might eventually replace the current gold standards. In this review, we discuss the feasibility of this approach and summarize the current evidence on AF detection with smartwatches.

On admission serum sodium and uric acid levels predict 30 day rehospitalization or death in patients with acute decompensated heart failure.

AIMS: A considerable proportion of hospitalized patients for acute decompensated heart failure will be readmitted or die in short-term follow-up. In the present study, we aimed to assess the role of admission sodium (Na) and uric acid (UA) levels in the prediction of 30 day post-discharge heart failure readmission or all-cause mortality in advanced heart failure patients admitted with acute decompensation. METHODS AND RESULTS: One hundred and forty consecutive advanced heart failure patients who were admitted for a recent cardiac decompensation were enrolled in this prospective study. Serum Na and UA levels remained statistically unchanged during index admission (P = 0. 54 and 0.19, respectively). Within 30 days post-discharge, composite end point of heart failure rehospitalization or all-cause death occurred in 62 (44.3%) patients (event group). Length of stay was statistically similar between patients in the event and non-event groups (P = 0.38). No correlations were also found between length of stay and left ventricular ejection fraction, serum Na, UA, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), creatinine, and N-terminal pro b-type natriuretic peptide (NT-proBNP) levels (all P > 0.05). Lower left ventricular ejection fraction and Na and higher UA on admission were significantly associated with 30 day event both in univariate and multivariate analyses. CONCLUSIONS: Given the predictive role of baseline Na and UA for early post-discharge outcome and the absence of significant changes in their levels during initial hospitalization, admission Na and UA can be considered as prognosticators of acute decompensated heart failure, which their prognostic significance cannot be affected by routine acute heart failure therapy.

Left ventricular systolic dysfunction in two patients with ankylosing spondylitis: What is the role of corticosteroids?

Ankylosing spondylitis (AS) is a chronic inflammatory condition that most commonly affects the axial skeleton. The most common cardiac manifestation in patients with AS is the aortic root and valve disease, followed by conduction and rhythm abnormalities, decreased coronary flow reserve, myocardial infarction, and diastolic dysfunction. However, the presence of systolic dysfunction has been less described in patients with AS. Herein we present two cases of idiopathic dilated cardiomyopathy in patients with AS. These patients were noted to have an improvement of their ejection fraction following treatment of AS. Clinical and echocardiographic improvement on anti-inflammatory treatment might be a clue to the inflammatory nature of this myocardial problem, and further investigations to study the issue is required.

Measurement of pulmonary arterial elastance in patients with systolic heart failure using Doppler echocardiography.

OBJECTIVE: A reliable and easy-to-perform method for measuring right ventricular (RV) afterload is desirable when scheduling patients with systolic heart failure to undergo heart transplantation. The present study aimed to investigate the accuracy of echocardiographically-derived pulmonary arterial elastance as a measurement of pulmonary vascular resistance by comparing it with invasive measures. METHODS: Thirty-one patients with moderate to severe systolic heart failure, including 22 (71%) male patients, with a mean age of 41.16 ± 15.9 years were enrolled in the study. Right heart catheterization and comprehensive echocardiography during the first hour after completion of cardiac catheterization were performed in all the patients. The pulmonary artery elastance was estimated using the ratio of end-systolic pressure (Pes) over the stroke volume (SV) by both cardiac catheterization [Ea (PV)-C] and echocardiography [Ea (PV)-E]. RESULTS: The mean Ea (PV)-C and Ea (PV)-E were estimated to be 0.73 ± 0.49 mm Hg/mL and 0.67 ± 0.44 mm Hg/mL, respectively. There was a significant relation between Ea (PV)-E and Ea (PV)-C (r=0.897, p<0.001). Agreement between echocardiography and catheterization methods for estimating Ea (PV), investigated by the Bland-Altman method, showed a mean bias of -0.06, with 95% limits of agreement from -0.36 mm Hg/mL to 0.48 mm Hg/mL. CONCLUSION: Doppler echocardiography is an easy, non-invasive, and inexpensive method for measuring pulmonary arterial elastance, which provides accurate and reliable estimation of RV afterload in patients with systolic heart failure.

An Intracardiac Mass in a Pregnant Woman Presenting With Ventricular Tachycardia.

A pregnant patient presented with symptomatic ventricular tachycardia. Echocardiography revealed a large intramyocardial mass. Surgical resection was attempted in conjunction with cryoablation of the surrounding myocardial tissue. Histologic examination of the resected mass revealed cardiac neurofibroma. To the best of our knowledge, this is the first report of cardiac neurofibroma in a pregnant patient in the absence of any neurocutaneous syndromes such as neurofibromatosis.

Prasugrel Results in Higher Decrease in High-Sensitivity C-Reactive Protein Level in Patients Undergoing Percutaneous Coronary Intervention Comparing to Clopidogrel.

OBJECTIVES: A growing body of clinical and laboratory evidence indicates that inflammation plays a crucial role in atherosclerosis. In the present study, we compared the effects of clopidogrel and prasugrel on high-sensitivity C-reactive protein (hs-CRP) in patients undergoing percutaneous coronary intervention (PCI). METHODS: The present randomized, double-blind clinical trial included 120 patients who underwent PCI. Eligible patients were randomly assigned 2:1 to one of the two groups: 80 patients in the first group received clopidogrel (Plavix(®); loading dose and maintenance dose of 300 and 75 mg daily, respectively) and 40 patients in the second group received prasugrel (Effient(®); loading dose and maintenance dose of 60 and 10 mg, respectively) for 12 weeks. The hs-CRP levels between baseline and 12th week were compared. RESULTS: Of the 120 patients, 69 patients (57.5%) were male. Pretreatment hs-CRP level was statistically comparable in clopidogrel (median, 15.10 mg/dL; interquartile range [IQR], 9.62-23.75 mg/dL) and prasugrel groups (median, 18 mg/dL; IQR, 14.25-22 mg/dL; P = 0.06). Patients taking clopidogrel showed a significant reduction in hs-CRP level compared with the baseline values (P < 0.001). Prasugrel administration also resulted in a significant reduction in hs-CRP level (P < 0.001). A significant 73% overall reduction in the hs-CRP level was seen with prasugrel compared with 39% overall reduction in hs-CRP level with clopidogrel (P = 0.002). CONCLUSION: Prasugrel seems to be superior to clopidogrel in the reduction of hs-CRP in patients undergoing PCI.

Changes of High Sensitivity C-Reactive Protein During Clopidogrel Therapy in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: The crucial role of inflammation in the development and progression of atherosclerosis has been previously described. However, there is insufficient data available to demonstrate the changes in high sensitivity C-reactive protein (hs-CRP) during clopidogrel therapy. OBJECTIVES: In the present study, we aimed to assess the changes in the inflammatory marker of coronary heart disease, i.e., hs-CRP during clopidogrel therapy, in patients undergoing percutaneous coronary intervention (PCI). We also evaluated the anti-inflammatory effects of clopidogrel, if any, in different groups of patients. PATIENTS AND METHODS: The study population included 650 consecutive patients who underwent elective, urgent, or emergent PCI. Patients received a 300-mg loading dose of clopidogrel (Plavix(®)) and aspirin either 24 hours before the planned PCI, or immediately before the procedure in patients with urgent or emergent PCI, followed by a 75-mg daily maintenance dose for up to 12 weeks. At the end of the 12(th) week, hs-CRP was re-assessed. RESULTS: Six hundred-fifty patients including 386 (59.4%) male and 264 (40.6%) female subjects were enrolled in the study. The mean hs-CRP level was 15.36 ± 9.83 mg/L with a median of 14 mg/L (interquartile range 8 to 19.6 mg/L). Female, hypertensive, diabetic, and non-smoking patients had higher reductions in hs-CRP in response to clopidogrel therapy compared to male, non-hypertensive, non-diabetic and smoker patients, respectively (all P < 0.005). The changes in the hs-CRP levels were also statistically different in patients with various index events before PCI (P < 0.001). No significant differences were observed in the mean reduction of hs-CRP between the patients without stent implantation and those with bare metal or drug-eluting stents (P = 0.07), respectively. CONCLUSIONS: We found that the use of clopidogrel in patients undergoing PCI had favorable effects on the suppression of hs-CRP. This effect appears to be heightened and more apparent in some group of patients with co-morbidities such as diabetes and hypertension.

Effects of triiodothyronine replacement therapy in patients with chronic stable heart failure and low-triiodothyronine syndrome: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: The present study assessed the changes in functional, biochemical, and echocardiographic measures following long-term liothyronine therapy in heart failure (HF) patients with low-triiodothyronine (T3) syndrome (LT3S). METHODS: In the present placebo-controlled, double-blind study, adult patients with clinically stable New York Heart Association functional class I-III systolic HF and LT3S receiving standard HF therapy were randomly assigned 1:1 to receive oral liothyronine or placebo for 6 weeks. Low-T3 syndrome was defined as a serum free T3 of less than the lower limit of normal (<2.4 pg/mL) with normal thyroid-stimulating hormone (thyrotropin) and free thyroxin values. RESULTS: Fifty patients, including 39 (78%) men with a mean ± standard deviation age of 60 ± 15 years were included. The 6-min walk distance increased in the liothyronine group by 93 ± 16 m and in the placebo group by 67 ± 28 m, resulting in a treatment effect of 26 m (P = 0.003). A higher decrease of high-sensitivity C-reactive protein level was seen in the liothyronine group than in the placebo group (P = 0.009). Liothyronine markedly decreased serum N-terminal pro-brain natriuretic peptide level compared with the placebo (P = 0.01). A significant increase was also seen in the left ventricular ejection fraction by liothyronine as compared with the placebo (<0.001). CONCLUSION: Triiodothyronine replacement by chronic liothyronine therapy seems to safely benefit stable HF patients with LT3S receiving optimal HF medications.

Metabolic Syndrome is Associated With Higher Wall Motion Score and Larger Infarct Size After Acute Myocardial Infarction.

BACKGROUND: Infarct size is an important surrogate end point for early and late mortality after acute myocardial infarction. Despite the high prevalence of metabolic syndrome in patients with atherosclerotic diseases, adequate data are still lacking regarding the extent of myocardial necrosis after acute myocardial infarction in these patients. OBJECTIVES: In the present study we aimed to compare myocardial infarction size in patients with metabolic syndrome to those without metabolic syndrome using peak CK-MB and cardiac troponin I (cTnI) at 72 hours after the onset of symptoms. PATIENTS AND METHODS: One-hundred patients with metabolic syndrome (group I) and 100 control subjects without metabolic syndrome (group II) who experienced acute myocardial infarction were included in the study. Diagnosis of metabolic syndrome was based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines published in 2001. Myocardial infarction size was compared between the two groups of patients using peak CK-MB and cTnI level in 72 hours after the onset of symptoms. RESULTS: Peak CK-MB and cTnI in 72 hours were found to be significantly higher in patients with metabolic syndrome compared with control subjects (both P < 0.001). Patients with metabolic syndrome also had markedly higher wall motion abnormality at 72 hours after the onset of symptoms as assessed by echocardiographically-derived Wall Motion Score Index (WMSI) (P < 0.001). Moreover, statistically significant relationships were found between WMSI and peak CK-MB and also cTnI at 72 hours (Spearman's rho = 0.56, P < 0.001 and Spearman's rho = 0.5, P < 0.001; respectively). However, association between WMSI and left ventricular ejection fraction was insignificant (Spearman's rho = -0.05, P = 0.46). CONCLUSIONS: We showed that patients with metabolic syndrome have larger infarct size compared to control subjects.

Anesthetic Management in a Patient With Type A Aortic Dissection and Superior Vena Cava Syndrome.

INTRODUCTION: Induction of general anesthesia in patients with superior vena cava (SVC) syndrome may cause airway obstruction and cardiovascular collapse. CASE PRESENTATION: Herein, we introduced a patient with the diagnosis of dissecting aneurysm of the ascending aorta who was candidate for emergency surgery. He also had symptoms of SVC syndrome. To maintain airway patency during anesthetic management, we decided to perform femoro-femoral cardiopulmonary bypass followed by general anesthesia and tracheal intubation. CONCLUSIONS: Femoro-femoral bypass prior to initiation of sternotomy is a safe and easy method in patients with aortic dissection and SVC syndrome in whom earlier endotracheal intubation may not be feasible.

Predictors of prolonged mechanical ventilation after open heart surgery.

INTRODUCTION: Due to the importance of prolonged mechanical ventilation (PMV) as a postoperative complication, predicting "high-risk" patients by identifying predisposing risk factors is of important issue. The present study was aimed to identify perioperative variables associated with PMV in patients undergoing open heart surgery. METHODS: A total of 743 consecutive patients, American Society of Anesthesiologists (ASA) physical status class III, who were scheduled to undergo open heart surgery using cardiopulmonary bypass were included in this observational study. Perioperative variables were compared between the patients with and without PMV, as defined by an extubation time of >48 h. RESULTS: PMV occurred in 45 (6.1%) patients. On univariate analysis, pre-operative variables; including gender, history of chronic obstructive pulmonary disease (COPD); chronic kidney disease and endocarditis, intra-operative variables; including type of surgery, operation time, pump time, transfusion in operating room and postoperative variables; including bleeding and inotrope-dependency were significantly different between patients with and without PMV (all P<0.001, except for COPD and transfusion in operating room; P=0.004 and P=0.017, respectively). CONCLUSION: Our findings reinforce that risk stratification for predicting delayed extubation should be an important aspect of preoperative clinical evaluation in all anesthesiology settings.