Morphogenetic adaptation of the looping embryonic heart to altered mechanical loads.

The biophysical mechanisms that drive and regulate cardiac looping are not well understood, but mechanical forces likely play a central role. Previous studies have shown that cardiac torsion, which defines left-right directionality, is caused largely by forces exerted on the heart tube by a membrane called the splanchnopleure (SPL). Here we show that, when the SPL is removed from the embryonic chick heart, torsion is initially suppressed. Several hours later, however, normal torsion is restored. This delayed torsion coincides with increased myocardial stiffness, especially on the right side of the heart. Exposure to the myosin inhibitor Y-27632 suppressed both responses, suggesting that the delayed torsion is caused by an abnormal cytoskeletal contraction. This hypothesis is supported further by computational modeling. These results suggest that the looping embryonic heart has the ability to adapt to changes in the mechanical environment, which may play a regulatory role during morphogenesis.     

Exploitation of host cell signaling machinery: activation of macrophage phosphotyrosine phosphatases as a novel mechanism of molecular microbial pathogenesis

Intracellular pathogens, particularly those that target host mononuclear phagocytes, have evolved strategies to either evade or inhibit cellular mechanisms of host defense. Mycobacterium tuberculosis and Leishmania donovani exemplify a diverse group of microorganisms that have developed the ability to invade and replicate within host macrophages, leading to disease expression. Recent studies have suggested that the pathogenesis of intracellular infection may involve interference with host cell signaling. Drawing upon examples from in vitro models that focused on M. tuberculosis and L. donovani, we review evidence that activation of host cell phosphotyrosine phosphatases may contribute to pathogenesis. A leading candidate appears to be the Src homology 2 domain containing phosphotyrosine phosphatase SHP-1, the activation of which may contribute to the development of infection and disease progression.     

Assessment of community contribution to the ICDS scheme in district Agra: a case study

This study was conducted to assess community contribution to the Integrated Child Development Services (ICDS) program, which promotes mother and child health in the Agra district, Uttar Pradesh, India. Three rural ICDS projects in the district were selected, out of which a total of 74 Anganwadi centers (AWCs) were chosen for the study. The Anganwadi workers (AWWs) were interviewed through a semi-structured questionnaire to assess the community?s contribution during the previous 6 months. Results revealed that about 68% of AWWs had been able to receive assistance in bringing the children to the AWC. 53.3% had received free accommodation for AWC, and 42.6% had obtained assistance in implementation of health activities. Only 4% and 12% of the AWWs reported community assistance in the preparation and distribution of nutritional supplements, respectively. There had been no contribution received in terms of raw food for supplementary nutrition and fuel for cooking. The study concludes that rural area free accommodation for the AWC and community assistance in bringing children to the AWC were the most common forms of community contribution to the ICDS program.     

Comparative trial of mexiletine and lignocaine in the treatment of early ventricular tachyarrhythmias after acute myocardial infarction

The antiarrhythmic effects of intravenously administered lignocaine and mexiletine were compared over a period of 48 hr in a randomized trial on 24 patients who developed ventricular tachyarrhythmias within 48 hr of the onset of acute myocardial infarction. Mexiletine was given as an initial bolus of 200 mg, followed by an infusion of 1 mg/min reduced to 0.5 mg/min after 1 hr. Lignocaine was given as a bolus of 100 mg, followed by an infusion of 3 mg/min reduced to 2 mg/min after 1 hr. Plasma levels of mexiletine, lignocaine, and monoethylglycinexylidide were monitored. The frequency of "complex" ventricular tachyarrhythmias was significantly lower in the mexiletine-treated group. This group of patients also had significantly fewer ventricular extrasystoles than those receiving lignocaine, the difference being most marked during the second 24 hr of treatment. Too few episodes of ventricular fibrillation occurred for statistical comment. The greater efficacy of mexiletine was not associated with increased drug toxicity.     

The Various Applications of 3D Printing in Cardiovascular Diseases

Purpose of Review

To highlight the various applications of 3D printing in cardiovascular disease and discuss its limitations and future direction.

Recent Findings

Use of handheld 3D printed models of cardiovascular structures has emerged as a facile modality in procedural and surgical planning as well as education and communication.

Summary

Three-dimensional (3D) printing is a novel imaging modality which involves creating patient-specific models of cardiovascular structures. As percutaneous and surgical therapies evolve, spatial recognition of complex cardiovascular anatomic relationships by cardiologists and cardiovascular surgeons is imperative. Handheld 3D printed models of cardiovascular structures provide a facile and intuitive road map for procedural and surgical planning, complementing conventional imaging modalities. Moreover, 3D printed models are efficacious educational and communication tools. This review highlights the various applications of 3D printing in cardiovascular diseases and discusses its limitations and future directions.

     

Prevalence of Noncardiac Multimorbidity in Patients Admitted to Two Cardiac Intensive Care Units and Their Association with Mortality

BackgroundCurrent cardiac intensive care unit (CICU) practice has seen an increase in patient complexity, including an increase in noncardiac organ failure, critical care therapies, and comorbidities. We sought to describe the changing epidemiology of noncardiac multimorbidity in the CICU population.MethodsWe analyzed consecutive unique patient admissions to 2 geographically distant tertiary care CICUs (n = 16,390). We assessed for the prevalence of 0, 1, 2, and ≥3 noncardiac comorbidities (diabetes, chronic lung, liver, and kidney disease, cancer, and stroke/transient ischemic attack) and their associations with hospital and postdischarge 1-year mortality using multivariable logistic regression.ResultsThe prevalence of 0, 1, 2, and ≥3 noncardiac comorbidities was 37.7%, 31.4%, 19.9%, and 11.0%, respectively. Increasing noncardiac comorbidities were associated with a stepwise increase in mortality, length of stay, noncardiac indications for ICU admission, and increased utilization of critical care therapies. After multivariable adjustment, compared with those without noncardiac comorbidities, there was an increased hospital mortality for patients with 1 (odds ratio [OR] 1.30; 95% confidence interval [CI], 1.10-1.54, P = .002), 2 (OR 1.47; 95% CI, 1.22-1.77, P < .001), and ≥3 (OR 1.79; 95% CI, 1.44-2.22, P < .001) noncardiac comorbidities. Similar trends for each additional noncardiac comorbidity were seen for postdischarge 1-year mortality (P < .001, all).ConclusionsIn 2 large contemporary CICU populations, we found that noncardiac multimorbidity was highly prevalent and a strong predictor of short- and long-term adverse clinical outcomes. Further study is needed to define the best care pathways for CICU patients with acute cardiac illness complicated by noncardiac multimorbidity.     

Novel ketoprofen–antioxidants mutual codrugs as safer nonsteroidal anti‐inflammatory drugs: Synthesis,kinetic and pharmacological evaluation

Ketoprofen belongs to one of the most common nonsteroidal anti‐inflammatory drugs (NSAIDs) but its clinical usefulness has been restricted due to the high incidence of gastrointestinal complications. The release of reactive oxygen species (ROS) in NSAIDs therapy plays a major role in causing gastric complications. Antioxidants not only prevent gastric ulceration and lipid peroxidation but also preserve glutathione‐type peroxidase (GPO) activity. Therefore, the present study investigates the utility of combining anti‐inflammatory and antioxidant properties of two different compounds in a single molecule to form a series of 16 ketoprofen–antioxidant mutual codrugs. The free carboxylic group, which is believed to be one of the reasons for gastric toxicity of ketoprofen, was masked temporarily by simple and double esterification with alcoholic/phenolic–OH of natural antioxidants. In simple esterification, ketoprofen is directly linked to natural antioxidants ( IIa–h ) in the hope to obtain drugs free of gastric side effects. In an attempt to improve the in vivo lability, as well as gastric side effects, the double ester codrugs, that is, ketoprofen–antioxidant through the glycolic acid spacer (–CH₂COO; IIIa–h ), have also been designed and synthesized. The synthesized codrugs were characterized by IR, ¹H NMR, ¹³C NMR, mass spectroscopy and elemental analysis. The in vitro hydrolysis studies showed the lowest hydrolysis (highest stability) in acidic pH 1.2, whereas moderate hydrolysis was seen at pH 7.4 and significant hydrolysis in 80% human blood plasma, as indicated by their t_1/2. The pharmacological evaluation results indicate that these ketoprofen–antioxidant mutual codrugs showed the retention of anti‐inflammatory and analgesic activity with a significant reduction in the ulcer index.