Miracle-dz/UniFAR-FTUs huggingface dataset:
Endogenous Opioids Do Not Mediate HCl-Induced Myocardial Dysfunction

ABSTRACT: We evaluated the hypothesis that increased endogenous opioid activity mediates part or all of the left ventricular contractile and pump dysfunction previously demonstrated in HCl-induced metabolic acidemia. Eighteen Western newborn lambs were catheterized and instrumented; pacing wires were sutured to the right atrial appendage; a catheter mounted micromanometer pressure transducer was inserted into the left ventricle; and a 2.5 F thermistor was inserted into the distal abdominal aorta. The lambs were studied 3 days after surgery. Metabolic acidemia was produced with an infusion of 0.5 N HCl into the inferior vena cava. Inhibition of endogenous opioids was achieved with a bolus of 2 mg/kg of intravenous naloxone, which was demonstrated to inhibit morphine sulfate-induced myocardial dysfunction. The effects of opioid inhibition were contrasted with our previously published results after restoration of a normal arterial pH with intravenous sodium bicarbonate. In agreement with our previous study, we found that reducing the arterial pH from 7.41 ± 0.01 to 6.97 ± 0.04 was associated with a 45% reduction in cardiac output which resulted from a 50% reduction in stroke volume. These changes in turn were mediated by a 35% reduction in the maximal first derivative of left ventricular pressure and/or a 63% increase in systemic vascular resistance which we used to estimate contractility and afterload, respectively. Left ventricular end diastolic pressure increased during acidemia. Although opioid inhibition produced a consistent increase in the maximal first derivative of left ventricular pressure, this increase was relatively small and was not associated with a significant change in cardiac output, stroke volume, or systemic vascular resistance. In contrast, restoration of a normal arterial pH was associated with increases in cardiac output, heart rate, stroke volume, and dP/dt to greater than control values, as well as a normalization of systemic vascular resistance. These hemodynamic changes were not attributable to direct effects of naloxone. Herein we suggest that although opioids may exert a small role in mediating the contractile dysfunction that occurs during HC- induced metabolic acidemia, there is no apparent influence of opioids on pump performance. Opioids participate very little in the myocardial dysfunction of this model of metabolic acidemia in lambs.
Protective effect of glucagon-like peptide-1 agents on reperfusion injury for acute myocardial infarction: a meta-analysis of randomized controlled trials

Abstract Background: The cardioprotective properties of glucagon-like peptide-1 (GLP-1) receptor agonists in acute myocardial infarction (AMI) patients against reperfusion injury remain unclear. We performed a meta-analysis to assess their role in the acute phase of AMI. Methods and results: Randomized controlled trials (RCTs) comparing GLP-1 agents with placebo in AMI patients undergoing percutaneous coronary intervention were identified by searching PubMed, Embase and Cochrane libraries. Six RCTs with 800 patients were included in the meta-analysis. Compared with placebo, GLP-1 agents improved left ventricular ejection fraction (LVEF) by 2.46 [95% confidence interval (CI): 0.23–4.70%] and reduced the infarct size in grams as well as in percentage of the area at risk [weighted mean difference (WMD) − 5.29, 95% CI: −10.39 to −0.19; WMD −0.08, 95% CI: −0.12 to −0.04, respectively]. The incidence of cardiovascular events appeared to be lower with GLP-1 therapy, but the statistical significance was not reached [relative risk (RR): 0.78; 95% CI: 0.58–1.06]. In terms of safety evaluation, GLP-1 treatment increased the risk of gastrointestinal adverse events (RR: 5.50, 95% CI: 2.85–10.60). Conclusions: Our analysis shows that in patients with AMI undergoing PCI, GLP-1 treatment is associated with improved LVEF and reduced infarct size.
Alpha radiation effects on n-i-p quantum dot epitaxial lift-off solar cells

Embedded nanostructures such as quantum dots (QDs) have been studied for many applications including enhanced mini-band absorption in intermediate-band solar cells and current matching in multi junction cells. Furthermore, solar cells with QDs have shown a radiation hardness and temperature tolerance that has been improved by adding nanostructures. InAs/GaAs QD cells were grown by MOVPE, fabricated and processed by epitaxial lift off, creating thin and flexible devices that exhibit enhanced sub-GaAs bandgap current collection. Due to the thinning of these devices, the sub-GaAs bandgap eternal quantum efficiency curves are more pronounced than those for a thicker cell, indicating the presence of a cavity mode effect. Champion devices incorporating QDs have short circuit currents exceeding those of baseline samples with no QDs by an absolute value of 0.12 mA/cm2 under 1-sun AM0 illumination. In addition to optical, materials, and electrical characterization, devices were exposed to alpha radiation to gauge the effects of a harmful environment on cell performance. In this area QD cells also outperformed baseline devices, with a relative end of life remaining maximum power factor increase of 10%.
PCNA clamp facilitates action of DNA cytosine methyltransferase 1 on hemimethylated DNA

Background: Proliferating cell nuclear antigen (PCNA) is a ring‐shaped protein known as a processivity factor of DNA polymerase δ. In addition to this role, PCNA interacts with a number of other proteins to increase their local concentration at replicated DNA sites. DNA cytosine methyltransferase 1 (Dnmt1), which preserves epigenetic signals by completing the methylation of hemimethylated DNA after DNA replication, has been indicated as one of these PCNA binding proteins by a previous work. However, the molecular mechanisms and functional significance of their association have not yet been studied.
Visualizing extravasation dynamics of metastatic tumor cells

Little is known about how metastatic cancer cells arrest in small capillaries and traverse the vascular wall during extravasation in vivo. Using real-time intravital imaging of human tumor cells transplanted into transparent zebrafish, we show here that extravasation of cancer cells is a highly dynamic process that involves the modulation of tumor cell adhesion to the endothelium and intravascular cell migration along the luminal surface of the vascular wall. Tumor cells do not damage or induce vascular leak at the site of extravasation, but rather induce local vessel remodeling characterized by clustering of endothelial cells and cell-cell junctions. Intravascular locomotion of tumor cells is independent of the direction of blood flow and requires β1-integrin-mediated adhesion to the blood-vessel wall. Interestingly, the expression of the pro-metastatic gene Twist in tumor cells increases their intravascular migration and extravasation through the vessel wall. However, in this case, Twist expression causes the tumor cells to switch to a β1-integrin-independent mode of extravasation that is associated with the formation of large dynamic rounded membrane protrusions. Our results demonstrate that extravasation of tumor cells is a highly dynamic process influenced by metastatic genes that target adhesion and intravascular migration of tumor cells, and induce endothelial remodeling.
Comparison of Frameless Stereotactic Systems: Accuracy, Precision, and Applications

OBJECTIVE Frameless stereotactic systems have become an integral part of neurosurgical practice. At our center, we recently introduced for clinical use a small, portable, frameless stereotactic system, namely the Cygnus PFS system (Compass International, Rochester, MN). The purpose of this study was to compare the accuracy of the Cygnus PFS system with that of two larger systems that are also currently in use at our institution, i.e., the SMN system (Zeiss, Oberkochen, Germany) and the ISG viewing wand (ISG Technologies, Toronto, Canada). These systems represent three kinds of frameless stereotactic technologies that are commercially available. Each system uses a different method of spatial localization, i.e., mechanical linkage (ISG system), magnetic field digitization (Cygnus system), or optical technology (SMN system). METHODS Using a stereotactic “phantom,” we measured the accuracies of all three systems with identical data sets. The errors in localization in three-dimensional space for nine targets were calculated by using 10 magnetic resonance imaging data sets. The precision of each system was also calculated. RESULTS With this experimental protocol, the Cygnus system attained a mean accuracy of 1.90 ± 0.7 mm, the ISG viewing wand system a mean accuracy of 1.67 ± 0.43 mm, and the SMN microscope a mean accuracy of 2.61 ± 0.99 mm. The precision values were not significantly different among the systems. CONCLUSION We observed only small differences in accuracy and precision among these three systems. We briefly review the advantages and disadvantages of each system and note that other factors, such as portability, ease of use, and microscope integration, should influence the selection of a frameless stereotactic system.
Magnetic Resonance Imaging Evaluation of Posterior Lumbar Interbody Fusion

Study Design. A prospective study investigated the use of magnetic resonance imaging (MRI) scanning in the assessment of posterior lumbar interbody fusion (PLIF) using carbon fiber cages. Objective. The aim of the study was to determine whether MRI scans in the coronal plane allow proper evaluation of interbody fusion through carbon cages. Summary of Background Data. Currently, there is no universally accepted radiologic assessment tool for evaluating fusion status after PLIF. Methods. Forty-nine levels of 47 patients were studied after PLIF using 98 carbon cages with MRI scans 24 months after surgery. These images were evaluated by two independent radiologists for bridging bony trabeculation through and surrounding the cages. Results. On coronal planes, the presence of bridging bony trabeculation through the cages was noted in 86 of 98 cages evaluated by observer 1 and 82 of 98 by observer 2. The bone bridging surrounding the cages was inhomogeneous. In six of 49 levels, the presence of low signal intensity zones at the cage end plate interface was observed by both radiologists, regarding three of 23 L4–L5 levels and three of 21 L5–S1 levels. Conclusions. The results of our study demonstrate that the most reliable radiographic indicator of fusion is the presence of bone bridging through the cages shown on coronal planes.
Dual-time-point FDG PET/CT for the evaluation of pediatric tumors.

OBJECTIVE The utility of dual-time-point (18)F-FDG PET/CT in differentiating benign from malignant processes in pediatric patients was assessed. SUBJECTS AND METHODS Twenty-one patients (13 girls and eight boys; age range, 1-17 years) with suspected malignancy underwent dual-time-point FDG PET/CT. Scan 1 was performed at approximately 60 minutes after i.v. injection of 5.18 MBq/kg of FDG, and scan 2 was performed at 121 ± 43 minutes after the first scan. Regions of interest were overlaid onto each non-attenuated-corrected image, and semiquantitative analysis was performed using the standardized uptake value (SUV) obtained from early and delayed images. A retention index was calculated according to the following equation: [(delayed SUV - early SUV) / early SUV] × 100. Results were compared prospectively in relation to pathologic examination or other conventional radiologic imaging or clinical follow-up. A retention index of 10% or higher was chosen as a cutoff for differentiating malignant from benign entities. RESULTS For patients with malignant disease, the average SUV increased from 7.3 ± 1.2 to 10.9 ± 2.7 between the two time points, whereas the SUV changed from 4.5 ± 0.8 to 4.2 ± 1.0 for patients with benign lesions. The average retention index was 37.1% ± 10.8% for patients with malignant lesions versus -9.9% ± 7.1% for benign lesions (p < 0.01). With a cutoff value of 10% or higher for the retention index, the sensitivity and specificity of dual-time-point FDG PET/CT were 77% and 80%, respectively. CONCLUSION These data show that dual-time-point FDG PET/CT is useful in distinguishing malignant from benign processes in pediatric patients.
Ketorolac is Not Nephrotoxic in Connection with Sevoflurane Anesthesia in Patients Undergoing Breast Surgery

Ketorolac, which may cause renal vasoconstriction by cyclooxygenase inhibition, is often administered to patients anesthetized with sevoflurane that is metabolized to inorganic fluoride (F-), another potential nephrotoxin. We assessed this possible interaction using urine N-acetyl-&bgr;-D-glucosaminidase indexed to urinary creatinine (U-NAG/crea) as a marker of proximal tubular, &bgr;2-microglobulin as a tubular, urine oxygen tension (PuO2) as a medullary, and erythropoietin as a marker of tubulointerstitial damage. Thirty women (ASA physical status I-II) undergoing breast surgery were included in our double-blinded study. They were allocated into two groups receiving either ketorolac 30 mg IM (Group K) or saline (Group C) at the time of premedication, at the end of, and 6 h after anesthesia maintained with sevoflurane. Urine output, U-NAG/crea, PuO2, serum creatinine, urea, and F- were assessed. Blood loss was larger in Group K (465 ± 286 mL vs 240 ± 149 mL, mean ± sd, P < 0.05). The MAC-doses of sevoflurane were similar. U-NAG/crea increased during the first 2 h of anesthesia and serum F- peaked 2 h after the anesthesia without differences between the groups. There were no statistically significant changes in PuO2, erythropoietin, &bgr;2-microglobulin, serum creatinine, urea, or urine output during anesthesia or the recovery period in either group. Our results indicate that the kidneys are not affected by ketorolac administered in connection with sevoflurane anesthesia.
Excess Postexercise Oxygen Consumption is Unaffected by the Resistance and Aerobic Exercise Order in an Exercise Session

Oliveira, NL and Oliveira, J. Excess postexercise oxygen consumption is unaffected by the resistance and aerobic exercise order in an exercise session. J Strength Cond Res 25(10): 2843–2850, 2011—The main purpose of this study was to compare the magnitude and duration of excess postexercise oxygen consumption (EPOC) after 2 exercise sessions with different exercise mode orders, resistance followed by aerobic exercise (R–A); aerobic by resistance exercise (A–R). Seven young men (19.6 ± 1.4 years) randomly underwent the 2 sessions. Aerobic exercise was performed on a treadmill for 30 minutes (80–85% of reserve heart rate). Resistance exercise consisted of 3 sets of 10 repetition maximum on 5 exercises. Previous to the exercise sessions, &OV0312;O2, heart rate, &OV0312;CO2, and respiratory exchange rate (RER) were measured for 15 minutes and again during recovery from exercise for 60 minutes. The EPOC magnitude was not significantly different between R–A (5.17 ± 2.26 L) and A–R (5.23 ± 2.48 L). Throughout the recovery period (60 minutes), &OV0312;O2 and HR values were significantly higher than those observed in the pre-exercise period (p < 0.05) in both exercise sessions. In the first 10 minutes of recovery, &OV0312;CO2 and RER declined to pre-exercise levels. Moreover, &OV0312;CO2 and RER values in A–R were significantly lower than in R–A. In conclusion, the main result of this study suggests that exercise mode order does not affect the EPOC magnitude and duration. Therefore, it is not necessary for an individual to consider the EPOC when making the decision as to which exercise mode is better to start a training session.
Vitamin D deficiency is associated with IL-6 levels and monocyte activation in HIV-infected persons

Background Immune activation plays a key role in HIV pathogenesis. Markers of inflammation have been associated with vitamin D deficiency in the general population. Studies have also demonstrated associations of vitamin D deficiency with increased risk of HIV progression and death. The relationship between persistent inflammation and immune activation during chronic HIV infection and vitamin D deficiency remains unclear. Methods Cryopreserved specimens were analyzed from 663 participants at the time of enrollment from the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) from 2004 to 2006. Biomarkers of inflammation, atherosclerosis, and coagulation were measured using enzyme-linked immunosorbent assays (ELISAs) and electrochemiluminescence. 25(OH)D, the stable precursor form of vitamin D, was measured using a radioimmunoassay with levels defined as: normal (≥30ng/mL), insufficient (20–29 ng/mL) and deficient (<20 ng/mL). Monocyte phenotypes were assessed by flow cytometry. Linear and logistic regression models were used to determine statistical associations between biomarkers and vitamin D deficiency. Results 25(OH)D levels were deficient in 251 (38%) participants, insufficient in 222 (34%), and normal in 190 (29%). Patients with vitamin D deficiency, when compared to those with insufficient or normal vitamin D levels, had increased levels of IL-6 (23%; p<0.01), TNF-α (21%, p = 0.03), D-dimer (24%, p = 0.01), higher proportions of CD14dimCD16+ (22%, p<0.01) and CX3CR1+ monocytes (48%; p<0.001) and decreased frequency of CCR2+ monocytes (-3.4%, p<0.001). In fully adjusted models, vitamin D associations with abnormal biomarker levels persisted for IL-6 levels and CX3CR1+ and CCR2+ phenotypes. Conclusions Vitamin D deficiency is associated with greater inflammation and activated monocyte phenotypes. The role of vitamin D deficiency in persistent immune activation and associated complications during chronic HIV disease should be further evaluated as a possible target for intervention.
Autoerotic Deaths in the Literature from 1954 to 2004: A Review

ABSTRACT: Autoerotic death by hanging or ligature is a method of autoeroticism well known by forensic pathologists. In order to analyze autoerotic deaths of nonclassic hanging or ligature type, this paper reviews all published cases of autoerotic deaths from 1954 to 2004, with the exclusion of homicide cases or cases in which the autoerotic activity was not solitary. These articles were obtained through a systematic Medline database search. A total of 408 cases of such deaths has been reported in 57 articles. For each case, the following characteristics are presented here: sex, age, race, method of autoerotic activity, cause of death, and location where the body was found. Autoerotic death practioners were predominantly Caucasian males. Victims were aged from 9 to 77 years and were mainly found in various indoor locations. Most cases were asphyxia by hanging, ligature, plastic bags, chemical substances, or a mixture of these. Still, atypical methods of autoerotic activity leading to death accounted for about 10.3% of cases in the literature and are classified here into five broad categories: electrocution (3.7%), overdressing/body wrapping (1.5%), foreign body insertion (1.2%), atypical asphyxia method (2.9%), and miscellaneous (1.0%). All these atypical methods are further discussed individually.
CYP2D in the brain.

CYP2D1, 2D2, 2D3, and 2D4 are major CYP2D isoforms expressed in the rat. In humans, only CYP2D6 is expressed. In rat brain, the mRNA for CYP2D4 is most abundant in cerebellum, striatum, pons and medulla oblongata. In human brain, CYP2D6 mRNA expression was detected in all regions with highest levels observed in cerebellum. CYP2D isoforms are involved in the metabolism of not only xenobiotics such as antidepressants, beta-adrenergic blockers, antiarrhysthmics, and antihypertensives, but also endogenous compounds such as trace amine and neurosteroids. Among 11 isoforms of human recombinant P450s, only CYP2D6 exhibited an ability to efficiently convert tyramine which exists in the brain, to dopamine. CYP2D4 and CYP2D6 which are the predominant CYP2D isoforms in the rat and human brain, respectively, possess 21-hydroxylation activity for both progesterone and allopregnanolone. CYP2D4, not P450c21, works as a steroid 21-hydroxylase in the brain. These results suggested that CYP2D in the brain may be involved in the metabolism of neuronal amines and steroids and in the regulation of the central nervous system.
Lipid altering-efficacy of ezetimibe co-administered with simvastatin compared with rosuvastatin: a meta-analysis of pooled data from 14 clinical trials

ABSTRACT Objective: Results of direct comparative studies between ezetimibe/simvastatin and rosuvastatin therapies have not been reported. Both of these treatment options offer significant reductions in LDL-C. To evaluate the lipid efficacy of each of these therapies relative to each other, a meta-analysis of data from 14 randomized, double-blind clinical trials that compared the effectiveness of two new options for cholesterol lowering was performed. Data sources: PubMed, EMBASE and BIOSIS databases were searched up to March 14, 2004. Methods of study selection: Efficacy results from clinical trials with the co-administration of ezetimibe 10 mg with simvastatin or with the ezetimibe/simvastatin combination product (ezetimibe/simvastatin 10/10 mg, 10/20 mg, 10/40 mg, and 10/80 mg) were compared with efficacy results from clinical trials of rosuvastatin 5 mg, 10 mg, 20 mg, and 40 mg in patients with primary hypercholesterolemia. Trials in healthy patients, heterozygous familial hypercholesterolemia or combined hyperlipidemia, and pharmacokinetic trials were excluded. Data extraction and synthesis: This analysis used pooled data for LDL-C, HDL-C, non-HDL-C, triglycerides, total cholesterol, apolipoprotein (apo) A-I, and apo B for the two therapies at their lowest doses (ezetimibe/simvastatin 10/10 mg and rosuvastatin 5 mg) through their highest doses (ezetimibe/simvastatin 10/80 mg and rosuvastatin 40 mg), and estimated within-treatment percentage changes in these parameters. Percentage reductions from baseline in LDL-C for the pooled data were 46.2% and 41.8% for ezetimibe/simvastatin 10/10 mg and rosuvastatin 5 mg, respectively; 50.6% and 47.4% for ezetimibe/simvastatin 10/20 mg and rosuvastatin 10 mg, respectively; 55.9% and 52.1% for ezetimibe/simvastatin 10/40 mg and rosuvastatin 20 mg, respectively; and 59.7% and 58.5% for ezetimibe/simvastatin 10/80 mg and rosuvastatin 40 mg, respectively. Conclusions: The results of this meta-analysis suggest greater LDL-C lowering with ezetimibe/simvastatin compared with rosuvastatin. These results need to be confirmed in a head-to-head comparison of both therapies.
Rough‐Form Lipopolysaccharide Increases Apoptosis in Human CD4+ and CD8+ T Lymphocytes

Immunosuppression induced by lymphocyte apoptosis is considered an important factor in the pathogenesis of sepsis and has been demonstrated in both animal models of lipopolysaccharide (LPS)‐induced endotoxemia and septic patients. As rough‐form LPS (R‐LPS) has recently been shown to elicit a stronger immunological response than regular smooth‐form LPS (S‐LPS), we aimed to assess the apoptosis‐inducing capabilities of R‐LPS in different subsets of lymphocytes (CD4+ T cells, CD8+ T cell, B cells and NK cells). Using multicolour flow cytometry on human peripheral blood mononuclear cells, we found that R‐LPS increased apoptosis in CD4+ and CD8+ T cells assessed by annexin V and propidium iodide (AV+PI−), compared with both S‐LPS‐stimulated and unstimulated cells. 7‐Amino‐actinomycin D and staining for intracellular active caspase‐3, which are considered later signs of apoptosis, did not reveal the same results. Both forms appeared to inhibit apoptosis in B cells, but no LPS‐form‐specific effect was seen on B or NK cells. Our results indicate that R‐LPS induces a stronger AV+PI−‐assessed apoptotic response in T cells than S‐LPS. Our findings emphasize the importance of T cell apoptosis in endotoxemia and advocates for control of LPS form in both endotoxemia research and clinical trials with Gram‐negative infections.