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.     

Pyridine: the scaffolds with significant clinical diversity

The nitrogen-bearing heterocycle pyridine in its several analogous forms occupies an important position as a precious source of clinically useful agents in the field of medicinal chemistry research. This privileged scaffold has been consistently incorporated in a diverse range of drug candidates approved by the FDA (Food and Drug Administration). This moiety has attracted increasing attention from several disease states owing to its ease of parallelization and testing potential pertaining to the chemical space. In the next few years, a larger share of novel pyridine-based drug candidates is expected. This review unifies the current advances in novel pyridine-based molecular frameworks and their unique clinical relevance as reported over the last two decades. It highlights an inclination to the use of pyridine-based molecules in drug crafting and the subsequent emergence of several potent and eligible candidates against a range of diversified diseases.

The nitrogen-bearing heterocycle pyridine in its several analogous forms occupies an important position as a precious source of clinically useful agents in the field of medicinal chemistry research.     

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.     

Admission Braden Skin Score Independently Predicts Mortality in Cardiac Intensive Care Patients

ObjectiveTo determine whether a low Braden skin score (BSS), reflecting increased risk for skin pressure injury, would predict lower survival in cardiac intensive care unit (CICU) patients after adjustment for illness severity and comorbidities.Patients and MethodsThis retrospective cohort study included consecutive unique adult patients admitted to a single tertiary care referral hospital CICU from January 1, 2007, through December 31, 2015, who had a BSS documented on CICU admission. The primary outcome was all-cause hospital mortality, using elastic net penalized logistic regression to determine predictors of hospital mortality. The secondary outcome was all-cause post-discharge mortality, using Cox proportional hazards models to determine predictors of post-discharge mortality.ResultsThe study included 9552 patients with a mean age of 67.4±15.2 years (3589 [37.6%] were females) and a hospital mortality rate of 8.3%. Admission BSS was inversely associated with hospital mortality (unadjusted odds ratio, 0.70; 95% CI, 0.68-0.72; P<.001; area under the receiver operator curve, 0.80; 95% CI, 0.78-0.82), with increased short-term mortality as a function of decreasing admission BSS. After adjustment for illness severity and comorbidities using multivariable analysis, admission BSS remained inversely associated with hospital mortality (adjusted odds ratio, 0.88; 95% CI, 0.85-0.92; P<.001). Among hospital survivors, admission BSS was inversely associated with post-discharge mortality after adjustment for illness severity and comorbidities (adjusted hazard ratio, 0.89; 95% CI, 0.88-0. 90; P<.001).ConclusionThe admission BSS, a simple inexpensive bedside nursing assessment potentially reflecting frailty and overall illness acuity, was independently associated with hospital and post-discharge mortality when added to established multiparametric illness severity scores among contemporary CICU patients.