Modulation of low-dose ozone and LPS exposed acute mouse lung inflammation by IF1 mediated ATP hydrolysis inhibitor, BTB06584.

Ozone and bacterial lipopolysaccharide (LPS) are common air pollutants that are related to high hospital admissions due to airway hyperreactivity and increased susceptibility to infections, especially in children, older population and individuals with underlying conditions. We modeled acute lung inflammation (ALI) by exposing 6-8 week old male mice to 0.005 ppm ozone for 2 h followed by 50 µg of intranasal LPS. We compared the immunomodulatory effects of single dose pre-treatment with CD61 blocking antibody (clone 2C9.G2), ATPase inhibitor BTB06584 against propranolol as the immune-stimulant and dexamethasone as the immune-suppressant in the ALI model. Ozone and LPS exposure induced lung neutrophil and eosinophil recruitment as measured by respective peroxidase (MPO and EPX) assays, systemic leukopenia, increased levels of lung vascular neutrophil regulatory chemokines such as CXCL5, SDF-1, CXCL13 and a decrease in immune-regulatory chemokines such as BAL IL-10 and CCL27. While CD61 blocking antibody and BTB06584 produced maximum increase in BAL leukocyte counts, protein content and BAL chemokines, these treatments induced moderate increase in lung MPO and EPX content. CD61 blocking antibody induced maximal BAL cell death, a markedly punctate distribution of NK1.1, CX3CR1, CD61. BTB06584 preserved BAL cell viability with cytosolic and membrane distribution of Gr1 and CX3CR1. Propranolol attenuated BAL protein, protected against BAL cell death, induced polarized distribution of NK1.1, CX3CR1 and CD61 but presented with high lung EPX. Dexamethasone induced sparse cell membrane distribution of CX3CR1 and CD61 on BAL cells and displayed very low lung MPO and EPX levels despite highest levels of BAL chemokines. Our study unravels ATPase inhibitor IF1 as a novel drug target for lung injury.

Spatio-temporal hybrid neural networks reduce erroneous human "judgement calls" in the diagnosis of Takotsubo syndrome.

BACKGROUND: We investigate whether deep learning (DL) neural networks can reduce erroneous human "judgment calls" on bedside echocardiograms and help distinguish Takotsubo syndrome (TTS) from anterior wall ST segment elevation myocardial infarction (STEMI). METHODS: We developed a single-channel (DCNN[2D SCI]), a multi-channel (DCNN[2D MCI]), and a 3-dimensional (DCNN[2D+t]) deep convolution neural network, and a recurrent neural network (RNN) based on 17,280 still-frame images and 540 videos from 2-dimensional echocardiograms in 10 years (1 January 2008 to 1 January 2018) retrospective cohort in University of Iowa (UI) and eight other medical centers. Echocardiograms from 450 UI patients were randomly divided into training and testing sets for internal training, testing, and model construction. Echocardiograms of 90 patients from the other medical centers were used for external validation to evaluate the model generalizability. A total of 49 board-certified human readers performed human-side classification on the same echocardiography dataset to compare the diagnostic performance and help data visualization. FINDINGS: The DCNN (2D SCI), DCNN (2D MCI), DCNN(2D+t), and RNN models established based on UI dataset for TTS versus STEMI prediction showed mean diagnostic accuracy 73%, 75%, 80%, and 75% respectively, and mean diagnostic accuracy of 74%, 74%, 77%, and 73%, respectively, on the external validation. DCNN(2D+t) (area under the curve [AUC] 0·787 vs. 0·699, P = 0·015) and RNN models (AUC 0·774 vs. 0·699, P = 0·033) outperformed human readers in differentiating TTS and STEMI by reducing human erroneous judgement calls on TTS. INTERPRETATION: Spatio-temporal hybrid DL neural networks reduce erroneous human "judgement calls" in distinguishing TTS from anterior wall STEMI based on bedside echocardiographic videos. FUNDING: University of Iowa Obermann Center for Advanced Studies Interdisciplinary Research Grant, and Institute for Clinical and Translational Science Grant. National Institutes of Health Award (1R01EB025018-01).

Acceptability of Mental Health Facilities and De-addiction Centers in India.

Not much is known about disease prevalence, treatment outcomes, trained manpower, programs, and patients' awareness of diseases from South Asia, compared with the Western world. While other aspects are improving, the quantitative evaluation of awareness of diseases is lagging. Compared with other diseases, the situation for mental health disorders and addiction is worse. While no single study can fully quantify all aspects of awareness, a good starting point is to understand if increasing the number of mental health facilities is beneficial by understanding people's perception toward the likelihood of contracting various diseases, their preferred approach to treatment, and their perception of whether there are enough current facilities. We surveyed over 8000 families across several states of India and asked if they would treat a particular problem at home, visit a local healer, seek religious council, or go to a modern hospital for treatment. Our questions also included non-medical options to assess how likely people are to avoid trained medical help. We also asked people about their perceived likelihood of a family member ever suffering from (1) diarrhea, (2) high fever, (3) alcoholism, and (4) schizophrenia and other mental health problems. We reversed the order of diseases in our questions for a fraction of the population to evaluate the effect of order of questioning. Finally, we asked, if people feel they have enough local healers, religious places, general hospitals, de-addiction centers, and mental health facilities. Despite the taboo around mental health, many people claimed that their family members were unlikely to contract mental health or addiction problems, people recognized the severe paucity of mental health facilities and de-addiction centers. This raises hope for improving the mental health situation in India. We also found a significant relation between education levels and choices people make, underscoring the positive role education has in improving mental health.

Peripheral interventions and antiplatelet therapy: Role in current practice.

Peripheral arterial disease (PAD) is a common disorder associated with a high risk of cardiovascular mortality and continues to be under-recognized. The major risk factors for PAD are similar to those for coronary and cerebrovascular disease. Management includes exercise program, pharmacologic therapy and revascularization including endovascular and surgical approach. The optimal revascularization strategy, endovascular or surgical intervention, is often debated due to the paucity of head to head randomized controlled studies. Despite significant advances in endovascular interventions resulting in increased utilization over surgical bypass, significant challenges still remain. Platelet activation and aggregation after percutaneous transluminal angioplasty of atherosclerotic arteries are important risk factors for re-occlusion/restenosis and life-threatening thrombosis following endovascular procedures. Antiplatelet agents are commonly prescribed to reduce the risk of myocardial infarction, stroke and death from cardiovascular causes in patients with PAD. Despite an abundance of data demonstrating efficacy of antiplatelet therapy in coronary artery disease and cerebrovascular disease, there is a paucity of clinical information, clinical guidelines and randomized controlled studies in the PAD population. Hence, data on antiplatelet therapy in coronary interventions is frequently extrapolated to peripheral interventions. The aim of this review article is to elucidate the current data on revascularization and the role and duration of antiplatelet and anticoagulant therapy in re-vascularized lower limb PAD patients.

Shorter Door-To-Balloon ST-Elevation Myocardial Infarction Time: Should There Be a Minimum Limit?

In ST-elevation myocardial infarction (STEMI) ischemic time is directly related to permanent myocardial damage and mortality. Therefore, it is crucial to restore myocardial perfusion rapidly. Door-to-balloon (DTB) time is defined as the duration between the arrival time of the patient to the medical facility until the time he or she is treated with percutaneous coronary intervention. Currently, DTB is the criterion that measures the quality of care provided to patients with STEMI at any given institution. It is well documented in the literature that longer DTB is associated with higher mortality; however, lowering DTB beyond current recommendations has not shown to decrease mortality rates. The current recommendations call for a DTB less than 90 minutes from the patient's first contact within the healthcare system, typically the arrival to the emergency department, to the time of the balloon inflation of the culprit coronary artery. Conversely, efforts to keep reducing DTB time may lead to unnecessary percutaneous coronary intervention (in false-positive STEMI) and delay appropriate therapy when needed, possibly missing an alternate potentially life-threatening diagnosis. In conclusion, we herein review the literature on DTB and mortality rate. We also make suggestions about ideal DTB time and hazards of shortening it beyond the recommended guidelines.

A rare cause of exercise induced ventricular tachycardia.

Coronary fistulas are anomalous shunts from a coronary artery to a cardiac chamber or great vessel, bypassing the myocardial circulation. A 42-year-old Asian man with no significant history of cardiac disease presented with exertional chest discomfort in the form of chest tightness over the precordial area. The patient had no cardiac risk factors, but given the duration and persistence of symptoms, we did a stress echocardiogram. The exercise led to a 'coronary artery steal phenomenon' caused by the coronary fistula, which diverted the blood from the left anterior descending artery to the pulmonary artery thereby producing the ischemic symptoms and ventricular tachycardia. Transcatheter coil embolization was unsuccessful, but the fistula was eventually closed surgically. A repeat stress echocardiogram before discharge was completely normal. We emphasize the need to individualize treatment, taking into consideration all factors in a particular patient.

Revascularization in Severe Left Ventricular Dysfunction: Does Myocardial Viability Even Matter?

Left ventricular dysfunction is a powerful prognostic predictor in patients with coronary artery disease and increasing number of patients with CAD and ischemic left ventricular (LV) dysfunction is a major clinical problem. Congestive heart failure is a frequent complication which is associated with significant health care costs and two-third of cases have ischemic cardiomyopathy. In such patients, coronary revascularization can lead to symptomatic and prognostic improvement and reversal of LV remodeling which led to the concept of viable myocardium to select patients in whom recovery of LV function and improvement of prognosis will outweigh the risk of surgical revascularization. The aim of this review article is to understand the different modalities for assessing myocardial viability and clinical impact of revascularization in relation to the evidence of viability in patients with LV dysfunction.