Out-of-hospital ventricular fibrillation in patients with acute myocardial infarction: coronary angiographic determinants

OBJECTIVES: The study intended to compare the acute coronary anatomy of patients with acute myocardial infarction (AMI) complicated by out-of-hospital ventricular fibrillation (VF) versus patients with AMI without this complication. BACKGROUND: More than half of the deaths associated with AMI occur out of the hospital and within 1 h of symptom onset. The angiographic determinants of out-of-hospital VF in patients with AMI have not been investigated in detail. METHODS: Acute coronary angiographic findings of 72 consecutive patients with AMI complicated by out-of-hospital VF were compared with findings from 144 matched patients with AMI without this complication. RESULTS: Patients with an acute occlusion of the left anterior descending coronary artery (LAD) or left circumflex coronary artery (LCx) had a higher risk for out-of-hospital VF compared with patients with an acute occlusion of the right coronary artery (RCA) (odds ratio and 95% confidence interval, respectively, 4.82 [2.35 to 9.92] and 4.92 [2.34 to 10.39]). With regard to extent of coronary artery disease (CAD), the location of the culprit lesion in the coronary arteries (proximal vs. mid or distal), the flow in the infarct related artery (IRA), the presence or absence of collaterals to the IRA and chronic occlusions, there were no differences between the two groups. CONCLUSIONS: Acute myocardial infarction due to occlusion in the left coronary artery (LCA) is associated with greater risk for out-of-hospital VF compared to the RCA. The location of occlusion within LCA (LAD, LCx, proximal or distal), amount of myocardium at risk for necrosis and extent of CAD are not related to out-of-hospital VF.     

Short- and long-term beneficial effects of trimetazidine in patients with diabetes and ischemic cardiomyopathy

Background

Trimetazidine (TMZ) has been shown to partially inhibit free fatty acid oxidation by shifting substrate utilization from fatty acid to glucose. The aim of this study was to assess the effects of TMZ in patients with diabetes and ischemic cardiomyopathy.

Methods

Sixteen patients with diabetes and ischemic hypokinetic cardiomyopathy (all males) on conventional therapy were randomized to receive either placebo or TMZ (20 mg 3 times per day), each arm lasting 15 days, and then again to receive either placebo or TMZ for 2 additional 6-month periods, according to a double-blind, crossover design. At the end of each period, all patients underwent exercise testing, 2-dimensional echocardiography, and hyperinsulinemic/euglycemic clamp. Among the others, New York Heart Association class, ejection fraction, exercise time, fasting blood glucose, end-clamp M value (index of total body glucose disposal) and endothelin-1 levels were evaluated.

Results

Both in the short and long term (completed by 13 patients), on TMZ compared to placebo, ejection fraction (47 ± 7 vs 41 ± 9 and 45 ± 8 vs 36 ± 8%, P < .001 for both) and M value (4.0 ± 1.8 vs 3.3 ± 1.6, P = .003, and 3.5 ± 1.5 vs 2.7 ± 1.6 mg/kg body weight/min, P < .01) increased, while fasting blood glucose (121 ± 30 vs 136 ± 40, P = .02 and 125 ± 36 vs 140 ± 43, P = .19) and endothelin-1 (8.8 ± 3.8 vs 10.9 ± 3.8, P < .001 and 6.2 ± 2.4 vs 9.2 ± 4.3 pg/mL, P = .03) decreased. In the short term, 10 patients decreased 1 class on the NYHA scale during treatment with TMZ (P = .019 vs placebo). Eight patients decreased 1 NYHA class while on long-term TMZ treatment, while on placebo 1 patient increased 1 NYHA class and none improved (P = .018 vs placebo).

Conclusions

In a short series of patients with diabetes and ischemic cardiomyopathy, TMZ improved left ventricular function, symptoms, glucose metabolism, and endothelial function. Shifting energy substrate preference away from fatty acid metabolism and toward glucose metabolism by TMZ appears an effective adjunctive treatment in patients with diabetes with postischemic cardiomyopathy.     

Kaposi’s sarcoma: a computational approach through protein–protein interaction and gene regulatory networks analysis

Interactomic data for Kaposi’s Sarcoma Associated Herpes virus (KSHV)—the causative agent of vascular origin tumor called Kaposi’s sarcoma—is relatively modest to date. The objective of this study was to assign functions to the previously uncharacterized ORFs in the virus using computational approaches and subsequently fit them to the host interactome landscape on protein, gene, and cellular level. On the basis of expression data, predicted RNA interference data, reported experimental data, and sequence based functional annotation we also tried to hypothesize the ORFs role in lytic and latent cycle during viral infection. We studied 17 previously uncharacterized ORFs in KSHV and the host-virus interplay seems to work in three major functional pathways—cell division, transport, metabolic and enzymatic in general. Studying the host-virus crosstalk for lytic phase predicts ORF 10 and ORF 11 as a predicted virus hub whereas PCNA is predicted as a host hub. On the other hand, ORF31 has been predicted as a latent phase inducible protein. KSHV invests a lion’s share of its coding potential to suppress host immune response; various inflammatory mediators such as IFN-γ, TNF, IL-6, and IL-8 are negatively regulated by the ORFs while Il-10 secretion is stimulated in contrast. Although, like any other computational prediction, the study requires further validation, keeping into account the reproducibility and vast sample size of the systems biology approach the study allows us to propose an integrated network for host-virus interaction with good confidence. We hope that the study, in the long run, would help us identify effective dug against potential molecular targets.     

Neurological disease caused by Oropouche virus in northern Brazil: should it be included in the scope of clinical neurological diseases?

Journal of NeuroVirology - We describe two neurological cases of Oropouche virus infection in northern Brazil, where the virus is endemic but neglected as a pathogen. This study reiterates the...     

Acyldepsipeptide activated ClpP1P2 macromolecule of Leptospira,an ideal Achilles’ heel to hamper the cell survival and deregulate ClpP proteolytic activity

Antibiotic acyldepsipeptide (ADEP) targets the bacterial ClpP serine protease and can inhibit the growth of numerous bacterial species by activating/dysregulating the protease activity within the cell. The spirochete Leptospira interrogans harbors two ClpP isoforms (LepClpP1 and LepClpP2). Supplementation of ADEP in the Leptospira growth medium resulted in the inhibition of bacterial growth. The ADEP mediated activation of the LepClpP mixture was dependent on the time allowed for the self-assembly of LepClpP1 and LepClpP2. The dynamic light scattering of the LepClpP mixture in the presence of the ADEP indicated a conformational transformation of the LepClpP machinery. Serine 98, a catalytic triad residue of the LepClpP1 in the LepClpP1P2 heterocomplex, was critical for the ADEP mediated activation. The computational prototype of the LepClpP1P2 structure suggested that the hydrophobic pockets wherein the ADEPs or the physiological chaperone ClpX predominantly dock are exclusively present in the LepClpP2 heptamer. Using the ADEP as a tool, this investigation provides an insight into the molecular function of the LepClpP1P2 in a coalition with its ATPase chaperone LepClpX. The shreds of the evidence illustrated in this investigation verify that ADEP1 possesses the ability to control the LepClpP system in an unconventional approach than the other organisms.     

Use of the composite asthma severity index in a pediatric subspecialty clinic

BackgroundThe Composite Asthma Severity Index (CASI) is a comprehensive tool to assess asthma severity, which has been applied in the research setting.ObjectiveTo evaluate, in an outpatient setting, whether a CASI score accurately predicts asthma severity or control as determined by means of subspecialist assessment. Asthma Control Test (ACT) and childhood ACT (C-ACT) scores were generated to provide additional context for CASI scores in relationship to assessments using another clinical tool.MethodsChildren aged 5 to 18 years with a physician diagnosis of persistent asthma were recruited from a tertiary care center. A pediatric pulmonologist made determinations on each participant’s asthma severity and control during a clinic visit. A CASI and ACT/C-ACT score was generated for each patient. Logistic regression and Spearman correlations were used to determine how well CASI scores predicted physician assessments. Agreement between ACT/C-ACT scores and physician assessment of asthma control was determined in supplemental analyses.ResultsCASI scores strongly predicted physician assessment of severity (Spearman correlation = 0.61, P < .001); unadjusted odds ratio (OR) equal to 36.67 (95% confidence interval [CI]: 8.83-152.34); and adjusted OR equal to 32.76 (95% CI: 85.70-188.44). In supplemental analyses, ACT/C-ACT scores strongly predicted physician assessment of control (Spearman correlation = 0.72, P < .001) with an unadjusted OR equal to 42.12 (95% CI: 13.34-133.00) and adjusted OR equal to 55.34 (95% CI: 13.62-224.89).ConclusionUse of the CASI was feasible and accurately predicted physician assessments of asthma severity and control in this sample, which are not distinct entities. The CASI is a robust tool that may be used successfully in ambulatory pediatric asthma care.     

Integration of light scattering with machine learning for label free cell detection

Light scattering has been used for label-free cell detection. The angular light scattering patterns from the cells are unique to them based on the cell size, nucleus size, number of mitochondria, and cell surface roughness. The patterns collected from the cells can then be classified based on different image characteristics. We have also developed a machine learning (ML) method to classify these cell light scattering patterns. As a case study we have used this light scattering technique integrated with the machine learning to analyze staurosporine-treated SH-SY5Y neuroblastoma cells and compare them to non-treated control cells. Experimental results show that the ML technique can provide a classification accuracy (treated versus non-treated) of over 90%. The predicted percentage of the treated cells in a mixed solution is within 5% of the reference (ground-truth) value and the technique has the potential to be a viable method for real-time detection and diagnosis.     

The Strongest Correlates of PTSD for Firefighters: Number,Recency, Frequency,or Perceived Threat of Traumatic Events?

Firefighters experience a wide range of traumatic events while on duty and are at risk to develop psychopathology and posttraumatic stress disorder (PTSD). According to cognitive models, the person's interpretation of the traumatic event is responsible for the development of PTSD rather than the traumatic event itself. This cross‐sectional study aimed to explore the contribution of perceived threat to explain PTSD symptoms in Portuguese firefighters, after adjusting for potential confounding factors. A sample of 397 firefighters completed self‐report measures of exposure to traumatic events, psychopathology, and PTSD. Perceived threat explained unique variance in PTSD symptoms, R² = .40, ΔR² = .02, F(10, 367) = 24.55, p < .001, Cohen's f² =.03, after adjusting for psychopathology, number, recency, and frequency of the events, and other potential confounding variables. The association between psychopathology and PTSD was also moderated by perceived threat, R² = .43, ΔR² = .03, F(11, 366) = 25.33, p < .001, Cohen's f² =.05. Firefighters may benefit from interventions that focus on perceived threat to prevent PTSD symptoms.