Pulmonary Matrix-derived Hydrogels from Patients with Idiopathic Pulmonary Fibrosis Induce a Proinflammatory State in Lung Fibroblasts In Vitro.

Idiopathic pulmonary fibrosis (IPF), one of the most common forms of interstitial lung disease, is a poorly understood, chronic, and often fatal fibroproliferative condition with only two FDA-approved medications. Understanding the pathobiology of the fibroblast in IPF is critical to evaluating and discovering novel therapeutics. Using a decellularized lung matrix derived from IPF patients, we generate three-dimensional (3D) hydrogels as in vitro models of lung physiology and characterize the phenotype of fibroblasts seeded into the hydrogels. When cultured in IPF ECM hydrogels, IPF fibroblasts display differential contractility compared to their normal counterparts, lose the classical myofibroblast marker α-smooth muscle actin, and increase expression of proinflammatory cytokines compared to fibroblasts seeded two-dimensionally (2D) on tissue culture dishes. We validate this proinflammatory state in fibroblast-conditioned media studies with monocytes and monocyte-derived macrophages. These findings add to a growing understanding of the lung microenvironment effect on fibroblast phenotypes, shed light on the potential role of fibroblasts as immune signaling hubs during lung fibrosis, and suggest intervention in fibroblast-immune cell crosstalk as a possible novel therapeutic avenue.

Curcumin induced oxidative stress attenuation by N-acetylcysteine co-treatment: a fibroblast and epithelial cell in-vitro study in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a fatal lung disease of unknown etiology with only two federally approved drug options. Given the complex molecular pathogenesis of IPF involving multiple cell types and multiple pathways, we explore the effects of a potential antifibrotic and antioxidant drug combination. Curcumin is a polyphenolic compound derived from turmeric with significant biological activity including a potential antifibrotic capacity. N-acetylcysteine (NAC) is a precursor to the antioxidant glutathione. To advance our understanding of these molecules, and to identify a clinical application, we present a small number of focused experiments that interrogates the effect of curcumin and NAC on pathways relevant to IPF in both fibroblasts and epithelial cells. METHODS: Primary epithelial cell and fibroblasts isolated from patients with IPF were challenged with a combination treatment of NAC and curcumin. Evaluation of the antifibrotic potential and effect on oxidative stress was performed through QPCR gene expression analysis and functional assays including scratch tests, viability assays, and measurement of induced reactive oxygen species. RESULTS: We demonstrate that curcumin alone does have antifibrotic potential, but that effect is accompanied by proapoptotic increases in oxidative stress. Coupled with this, we find that NAC alone can reduce oxidative stress, but that epithelial cell viability is decreased through this treatment. However, co-administration of these two molecules decreases oxidative stress and maintains high cell viability in both cell types. In addition, this co-treatment maintains an antifibrotic potential. CONCLUSIONS: These findings suggest a novel application for these molecules in IPF and encourage further exploration of this potential therapeutic approach.

Development and quantification of measures for risky and delayed food and monetary outcome choices.

Probability discounting (PD) measures risky choice patterns between smaller, more certain vs. larger, less certain outcomes. PD is associated with obesity as well as higher intake of foods high in fat and sugar. We developed and validated a brief PD task specifically for food-related choices-the Probabilistic Food Choice Questionnaire (PFCQ). We also validated a brief, existing PD monetary measure, the Probabilistic Monetary Choice Questionnaire (PMCQ) by comparing it to a titrating PD task. Participants (N = 110) were randomly assigned to either a food or money condition. Those assigned to the food condition completed the PFCQ and a more established, adjusting-amount PD task for hypothetical food outcomes. Those assigned to the money condition completed the PMCQ and a more established, adjusting-amount PD task. Participants also completed delay discounting (DD) tasks for the same outcome commodity. The PFCQ and adjusting-amount PD tasks strongly correlated across three magnitudes suggesting that the PFCQ may be a satisfactory and briefer measure for risky food choice. The PMCQ also showed significant correlations with the adjusting-amount monetary PD task, supporting its use for a brief measure of monetary discounting. For DD, the choice questionnaires demonstrated significant correlations with the adjusting-amount DD procedures, replicating previous research.

Improvements to surrogate data methods for nonstationary time series.

The method of surrogate data has been extensively applied to hypothesis testing of system linearity, when only one realization of the system, a time series, is known. Normally, surrogate data should preserve the linear stochastic structure and the amplitude distribution of the original series. Classical surrogate data methods (such as random permutation, amplitude adjusted Fourier transform, or iterative amplitude adjusted Fourier transform) are successful at preserving one or both of these features in stationary cases. However, they always produce stationary surrogates, hence existing nonstationarity could be interpreted as dynamic nonlinearity. Certain modifications have been proposed that additionally preserve some nonstationarity, at the expense of reproducing a great deal of nonlinearity. However, even those methods generally fail to preserve the trend (i.e., global nonstationarity in the mean) of the original series. This is the case of time series with unit roots in their autoregressive structure. Additionally, those methods, based on Fourier transform, either need first and last values in the original series to match, or they need to select a piece of the original series with matching ends. These conditions are often inapplicable and the resulting surrogates are adversely affected by the well-known artefact problem. In this study, we propose a simple technique that, applied within existing Fourier-transform-based methods, generates surrogate data that jointly preserve the aforementioned characteristics of the original series, including (even strong) trends. Moreover, our technique avoids the negative effects of end mismatch. Several artificial and real, stationary and nonstationary, linear and nonlinear time series are examined, in order to demonstrate the advantages of the methods. Corresponding surrogate data are produced with the classical and with the proposed methods, and the results are compared.

Glucose control and outcome in patients with stable diabetes and previous coronary, cerebrovascular or peripheral artery disease. Findings from the FRENA Registry.

AIM: The aim of this study was to address the controversy over the influence of intensive glucose control on the risk for cardiovascular events in patients with Type 2 diabetes. METHODS: FRENA is an ongoing registry of stable outpatients with symptomatic coronary artery disease, cerebrovascular disease or peripheral artery disease. We compared the incidence of subsequent ischaemic events (myocardial infarction, stroke or critical limb ischaemia) in patients with Type 2 diabetes and mean HbA(1c) levels < 7.0% (< 53 mmol/mol) vs. those with HbA(1c) levels > 7.0% (> 53 mmol/mol). RESULTS: Of 974 patients with Type 2 diabetes, 480 (49%) had mean HbA(1c) levels < 7% (< 53 mmol/mol). Over a mean follow-up of 14 months, 126 patients (13%) had subsequent ischaemic events: myocardial infarction (43), stroke (29) and critical limb ischaemia (64). The incidence of subsequent ischaemic events was significantly lower in patients with mean HbA(1c) levels < 7.0% (< 53 mmol/mol) than in those with HbA(1c) levels > 7.0% (> 53 mmol/mol) (8.6 vs. 14 per 100 patient-years; rate ratio 0.6; 95% CI 0.4-0.9). These differences persisted after adjusting for potential confounders. However, this better outcome was only found in patients presenting with coronary artery disease (rate ratio 0.4; 95% CI 0.2-0.8), not in those with cerebrovascular disease (rate ratio 0.9; 95% CI 0.4-2.0) or peripheral artery disease (rate ratio 0.8; 95% CI 0.5-1.3). Patients with mean HbA(1c) levels < 7.0% (< 53 mmol/mol) also had a lower mortality (rate ratio 0.6; 95% CI 0.3-0.99). CONCLUSIONS: In secondary prevention, patients with diabetes and HbA(1c) levels < 7.0% (< 53 mmol/mol) had a lower incidence of subsequent ischaemic events and a lower mortality than those with HbA(1c) levels > 7.0% (> 53 mmol/mol). These differences appeared only in patients with coronary artery disease.

Bone mass, bone mineral density and muscle mass in professional golfers.

The aim of this study was to determine the effects of long-term professional golf participation on whole-body and regional bone mass and density. Dual-energy X-ray absorptiometry was performed on 15 male professional golfers and 18 sedentary individuals, matched for sex, race, age (29+/-1 and 25+/-1 years, respectively), body mass (79+/-2 and 74+/-2 kg), height (1.78+/-0.01 and 1.77+/-0.02 m) and percent body fat (20+/-2 and 21+/-2%; mean +/- sx). We found that long-term professional golf participation is not associated with significant increments in regional or whole-body bone mass or density. Neither the lumbar spine nor the femoral neck showed any noticeable enhancement of bone mass in professional golfers compared with controls from the same population. The only effect of professional golf participation on regional body composition was a 9% increase in muscle mass in the dominant arm (P < 0.05).

Bovine leukaemia-virus infection in Costa Rica.

The geographical distribution of bovine leukaemia-virus (BLV)-infected herds in Costa Rica and the isolation of BLV from cases of enzootic bovine leukosis are presented. It was found that BLV is prevalent throughout the country, affecting mostly dairy cattle (Bos taurus) located in the highlands around the central valley of Costa Rica. By contrast, beef cattle (Bos indicus) raised in the lowlands were affected to a lesser extent. One out of four isolates of BLV obtained from local cattle with lymphosarcomatous tumours was analysed and had similar physical, serological and biological characteristics to a reference strain of BLV isolated in the USA. However, different patterns of recognition of BLV-protein p24 were observed among naturally infected cattle using the western-blotting technique.

A study of pediatric house staff's knowledge of pulse oximetry.

OBJECTIVE: Pulse oximetry is widely used to measure oxygen saturation in inpatient and outpatient settings. As with any medical technology, competence in interpretation and application of the data is essential for patient care. We therefore undertook a study to quantify pediatric house staff's knowledge of pulse oximetry and their ability to interpret the information. METHODS: A 16-item multiple choice questionnaire (6 demographic, 10 knowledge) was developed to assess knowledge of pulse oximetry. The questionnaire was administered to a total of 134 pediatric house staff from five medical school-affiliated residency programs in New York City. RESULTS: The mean test score and standard deviation was 64.3% +/- 1.9, with a range of 10% to 100%. Regarding three questions related to the knowledge of the oxyhemoglobin deviation curve, only 17% of the the respondents answered all three questions correctly. In three questions pertaining to the accuracy of the pulse oximeter, 36% of the respondents answered all questions correctly. Forty-three percent of the house staff believed that training in the use of pulse oximetry was inadequate. CONCLUSIONS: The results showed that there is marked variability in pediatric house staff's knowledge of all aspects of pulse oximetry. This could contribute to patient morbidity. We suggest that medical schools and residency programs place more emphasis on teaching the principles and applications of pulse oximetry and the oxyhemoglobin dissociation curve.

[Electrocardiogram of the healthy premature infant]. / El electrocardiograma del recién nacido prematuro sano.

At the Hospital de Ginecobstetricia del Centro Médico "La Raza", were taken EKG to 30 healthy premature newborn during a six month period. The first EKG was recorded 3 hours after birth, the second in 8 hours, the third in 24 h, the fourth in 48 h, the fifth in 72 hours, the sixth at the end of the first week, the seventh at the fifteen days and the eighth at 30 days after birth. The mean heart rate was 135 +/- 10 beats/min in the first week. There were heart rate elevation for the first three days after birth. The QRS mean axis were + 130 +/- 25 degrees, without changes during the study time. The QTc interval in all cases was higher than 0.42 sec. The voltage of waves R and S at right and left precordial leads were similar. At this gestational age the ventricular masses are equals. The T waves changes reflected hemodynamic changes. It is concluded what the healthy premature newborn had a typical EKG as a reflex to the cardiocirculatory adaptations.

[Percutaneous transluminal angioplasty using balloon catheter in a Blalock-Taussig pulmonary-systemic fistula]. / Angioplastia transluminal percutánea con catéter de globo en una fístula sistémico-pulmonar de Blalock-Taussig.

Percutaneous transluminal balloon angioplasty has been used successfully in the treatment of valvular and vascular stenosis. This article describes our experience with this technique to improve pulmonary blood flow in a patient with a severely stenotic Blalock-Taussig (B-T) systemic-to-right pulmonary artery anastomosis, with improvement in oxygen peripheric saturation from 33 to 78% immediately postdilatation and 69% three months later. Hemoglobin decreased from 20.4 to 18.9 gm/dl and hematocrit from 64% to 58.5%. In conclusion we think that this technique is an alternative instead of cardiac surgery, in these cases the procedure is only palliative.

[Rhabdomyoma in a newborn infant. Echocardiographic diagnosis]. / Rabdomioma en un recién nacido. Diagnóstico ecocardiográfico.

With the 2D echocardiography, is easier the diagnosis of intracardiac tumors nowadays. We present a case of a newborn girl with a rhabdomyoma intra-myocardiac and intracavitary. We discuss the clinical manifestations, surgical indications and the association with tuberous sclerosis.