Miracle-dz/UniFAR-FTUs huggingface dataset:
Protection against endotoxemia‐induced contractile dysfunction in mice with cardiac‐specific expression of slow skeletal troponin I

Gram negative endotoxemia is associated with an intrinsic impairment of cardiomyocyte contraction, in part due to a reduction in myofilament Ca2+ responsiveness. Endotoxemic rat hearts show increased cardiac troponin I (cTnl) phosphorylation at serines 23 and 24, residues required for the protein kinase A (PKA)‐dependent reduction of myofilament Ca2+ sensitivity after β‐adrenoceptor stimulation. To investigate the functional significance of increased TnI phosphorylation in endotoxemia, we studied the contractile effects of systemic bacterial lipopolysaccharide (LPS) treatment in transgenic mice (TG) with cardiac‐specific replacement of cTnI by slow skeletal TnI (ssTnI, which lacks the PKA phosphorylation sites) and matched nontransgenic littermates (NTG) on a CD1 background. In wild‐type CD1 mice treated with LPS (6 mg/kg ip), after 16–18 h there was a significant reduction in the maximum rates of left ventricular pressure development and pressure decline in isolated Langendorff‐perfused hearts compared with saline‐treated controls and a decrease in isolated myocyte unloaded sarcomere shortening from 6.1 ± 0.2 to 3.9 ± 0.2% (1 Hz, 32°C, P<0.05). Similarly, in NTG myocytes, endotoxemia reduced myocyte shortening by 42% from 6.7 ± 0.2 to 3.9 ± 0.1% (P<0.05) with no change in intracellular Ca2+ transients. However, in the TG group, LPS reduced myocyte shortening by only 13% from 7.5 ± 0.2 to 6.5 ± 0.2% (P<0.05). LPS treatment significantly reduced the positive inotropic effect of isoproterenol in NTG myocytes but not in TG myocytes, even though isoproterenol‐induced increases in Ca2+ transient amplitude were similar in both groups. Only LPS‐treated NTG hearts showed a significant increase in cTnI phosphorylation. Investigation of the sarcomere shortening‐Ca2+ relationship in Triton‐skinned cardiomyocytes revealed a significant reduction in myofilament Ca2+ sensitivity after LPS treatment in NTG myocytes, an effect that was substantially attenuated in TG myocytes. In conclusion, the replacement of cTnI with ssTnI in the heart provides significant protection against endotoxemia‐induced cardiac contractile dysfunction, most probably by preserving myofilament Ca2+ responsiveness due to prevention of phosphorylation of TnI at PKA‐sensitive sites.
Transcatheter Arterial Chemoembolization (TACE) in Hepatocellular Carcinoma (HCC): The Role of Angiogenesis and Invasiveness

OBJECTIVE:Although transcatheter arterial chemoembolization (TACE) is effective in hepatocellular carcinoma (HCC), it is not considered a curative procedure. Among the factors potentially interfering with its effectiveness is a hypothetical neoangiogenic reaction due to ischemia. In our study, we evaluated the changes in the levels of two angiogenic factors (vascular endothelial growth factor [VEGF] and basic fibroblast growth factor [b-FGF]) and one parameter of invasiveness (urokinase-type plasminogen activator [uPA]) in patients treated with TACE.METHODS:Three blood samples were provided from 71 HCC patients undergoing TACE: before TACE (t0), after 3 days (t1), and after 4 wk, when they had spiral computed tomography (sCT) scanning (t2). The referring radiologists blindly evaluated tumor burden and vascularization at t0 and residual activity at t2. The choice of TACE as treatment was based on the American Association for the Study of Liver Diseases (AASLD) guidelines.RESULTS:Complete response at sCT was recorded in 27% of patients; mean survival was 35 months (confidence interval [CI] 31–40) and the 4-yr survival was 57%. VEGF levels were significantly correlated with the number of nodes and were higher in nonresponders at t2 (P = 0.01); below-median VEGF levels predicted a longer survival (P = 0.008). b-FGF correlated with VEGF, tumor size, vascularization, and residual activity, showing a borderline correlation with survival. uPA correlated with tumor size and VEGF. VEGF was singled out in the Cox multivariate analysis as an independent predictor of survival.CONCLUSIONS:When TACE is not totally effective, it may induce a significant neoangiogenetic reaction, as suggested by an increase in VEGF and b-FGF following treatment; this affects patient survival. VEGF emerges as the most reliable prognostic parameter, so it could be measured for judging TACE efficacy. Finally, antiangiogenic drugs may be indicated in TACE-treated HCC.
A novel low‐molecular weight inhibitor of focal adhesion kinase, TAE226, inhibits glioma growth

Glioblastomas are highly lethal cancers that resist current therapies. Novel therapies under development target molecular mechanisms that promote glioblastoma growth. In glioblastoma patient specimens, the non‐receptor tyrosine kinase focal adhesion kinase (FAK) is overexpressed. Upon growth factor receptor stimulation or integrin engagement, FAK is activated by phosphorylation on critical tyrosine residues. Activated FAK initiates a signal transduction cascade which promotes glioma growth and invasion by increasing cellular adhesion, migration, invasion, and proliferation. We find that human glioma cell lines express different levels of total FAK protein and activating phosphorylation of tyrosine residues Tyr397, Tyr861, and Tyr925. As all glioma cell lines examined expressed phosphorylated FAK, we examined the efficacy of a novel low‐molecular weight inhibitor of FAK, TAE226, against human glioma cell lines. TAE226 inhibited the phosphorylation of FAK as well as the downstream effectors AKT, extracellular signal‐related kinase, and S6 ribosomal protein in multiple glioma cell lines. TAE226 induced a concentration‐dependent decrease in cellular proliferation with an associated G2 cell cycle arrest in every cell line and an increase in apoptosis in a cell‐line‐specific manner. TAE226 also decreased glioma cell adhesion, migration, and invasion through an artificial extracellular matrix. Together, these data demonstrate the potential benefit of TAE226 for glioma therapy. © 2007 Wiley‐Liss, Inc.
Are coagulation studies on blood sampled from arterial lines valid?

Coagulation tests were performed on two venous blood samples and two blood samples from arterial lines taken from 79 patients on an intensive care unit. For the first arterial sample the discard volume was 4.5 ml and for the second arterial sample the discard volume was 16 ml. From each pair of venous samples a mean venous coagulation value was calculated. There were statistically significant differences between arterial and venous results and between the two arterial samples for activated partial thromboplastin time and thrombin time assays but not for prothrombin time, reptilase time and fibrinogen assays. However, these differences were sufficiently small to be of little clinical significance. The bias for the difference in activated partial thromboplastin time values between the first arterial sample and the venous sample was +1.24 s (limits of agreement: −4.39 to +6.87 s) and between the second arterial sample and the venous sample the bias was +0.89 s (limits of agreement: −3.25 to +5.03 s). Only 3.8% of first arterial samples and 1.3% of second arterial samples produced activated partial thromboplastin time values that were more than 10% longer than the corresponding venous values. No heparin was detectable in these arterial samples using a heparin assay (< 0.02 iu.ml−1). The differences between arterial and venous activated partial thromboplastin times were slightly but not significantly greater in subgroups of patients with moderately or severely deranged coagulation compared with a group with normal coagulation. We conclude that samples from arterial lines provide valid activated partial thromboplastin time results using a discard volume of either 4.5 ml or 16 ml.
Elevated heart rate variability in physically active young and older adult women.

1. Low heart rate variability is associated with an increased risk of cardiac sudden death, coronary heart disease and all-cause mortality. We have previously shown that physically active postmenopausal women demonstrate higher levels of heart rate variability and cardiac baroreflex sensitivity compared to their sedentary peers. The purpose of the present prospective study was to test the hypothesis that heart rate variability and cardiac baroreflex sensitivity would be reduced with age in sedentary but not physically active women. To accomplish this, we measured heart rate variability (both time and frequency domain) and spontaneous cardiac baroreflex sensitivity (SBRS, sequence method) in the sitting posture in 23 sedentary women [11 premenopausal and 12 postmenopausal (age, 28 +/- 1 and 61 +/- 2 years; VO2max, 35.3 +/- 1.4 and 21.7 +/- 1.5 ml.min-1.kg-1 respectively] and in 22 physically active women [12 premenopausal and 10 postmenopausal (age, 31 +/- 1 and 59 +/- 2 years; VO2max, 52.5 +/- 1.4 and 39.7 +/- 1.8 ml.min-1.kg-1)]. 2. The S.D. of the R-R interval (time domain) was reduced (P < 0.05) with age in both sedentary (52 +/- 6 versus 33 +/- 4 ms) and physically active women (72 +/- 8 versus 49 +/- 9 ms). The high-frequency power (3740 +/- 1527 versus 915 +/- 188 and 9516 +/- 2849 versus 2803 +/- 1083 ms2/Hz), total power of heart rate variability and SBRS (11 +/- 2 versus 7 +/- 2 and 19 +/- 3 versus 13 +/- 2 ms/mmHg) also demonstrated similar age-related reductions in sedentary and physically active women, respectively (all P < 0.05). The S.D. of the R-R interval, high-frequency and total power of heart rate variability, and SBRS were higher (all P < 0.05) in the physically active compared with the sedentary women at any age. There was no significant influence of age or physical activity status on the low-frequency power of heart rate variability. In addition, no significant differences in any of the time or frequency domain measures of heart rate variability or SBRS were observed in users compared with non-users of hormone replacement therapy. 3. The results of the present study suggest that heart rate variability and cardiac baroreflex sensitivity decline similarly with age in healthy sedentary and physically active women. However, physically active women demonstrate higher levels of heart rate variability and cardiac baroreflex sensitivity compared with their sedentary peers, regardless of age.
Diagnostic Value of Gadoxetic Acid-Enhanced MR Imaging to Distinguish HCA and Its Subtype from FNH: A Systematic Review

Objective: The purpose of this study was to systematically review the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI) for differentiation of hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH), as well as HCA classification by using the low signal intensity (SI) in the hepatobiliary phase (HBP). Methods: A systematic process was used to review all published data in MEDLINE database about Gd-EOB-DTPA-MRI applied to differentiation of HCA and FNH, and classification of HCA by using low SI in the HBP. The pooled sensitivity and specificity were calculated to assess the diagnostic value of low SI in the HBP. Results: A review of 45 articles identified 10 eligible studies with a total of 288 HCA lesions. The pooled proportion of low SI in the HBP of HCA were 91% (95% CI: 0.81-0.97). In specific, the subtypes of HCA were 75% (95% CI: 0.64-0.85) for I-HCA, 100% (95% CI: 0.95-1.00) for H-HCA, 92% (95% CI: 0.70-1.00) for U-HCA, and 59% (95% CI: 0.00-1.00) for b-HCA, respectively. The pooled specificity and sensitivity of low SI in the HBP for distinguishing FNH from HCA were 95% (95% CI: 0.92-0.98) and 92% (95% CI: 0.87-0.96), respectively. Conclusion: Low SI in the HBP of Gd-EOB-DTPA-MRI is associated with higher accuracy for distinguishing HCA from FNH. However, the diagnostic accuracy may be overvalued, especially for the diagnosis of subtypes of b-HCA and I-HCA. Therefore, the risk factors and conventional imaging findings should be take into account simultaneously.
Forsythiae Fructus: A Review on its Phytochemistry, Quality Control, Pharmacology and Pharmacokinetics

Forsythiae Fructus, as a traditional Chinese medicine, has been widely used both as a single herb and in compound prescriptions in Asia, mainly due to its heat-clearing and detoxifying effects. Modern pharmacology has proved Forsythiae Fructus possesses various therapeutic effects, both in vitro and in vivo, such as anti-inflammatory, antibacterial and antiviral activities. Up to now, three hundred and twenty-one compounds have been identified and sensitive analytical methods have been established for its quality control. Recently, the pharmacokinetics of Forsythiae Fructus and its bioactive compounds have been reported, providing valuable information for its clinical application. Therefore, this systematic review focused on the newest scientific reports on Forsythiae Fructus and extensively summarizes its phytochemistry, pharmacology, pharmacokinetics and standardization procedures, especially the difference between the two applied types—unripe Forsythiae Fructus and ripe Forsythiae Fructus—in the hope of providing a helpful reference and guide for its clinical applications and further studies.
Short‐term sprint interval versus traditional endurance training: similar initial adaptations in human skeletal muscle and exercise performance

Brief, intense exercise training may induce metabolic and performance adaptations comparable to traditional endurance training. However, no study has directly compared these diverse training strategies in a standardized manner. We therefore examined changes in exercise capacity and molecular and cellular adaptations in skeletal muscle after low volume sprint‐interval training (SIT) and high volume endurance training (ET). Sixteen active men (21 ± 1 years, ) were assigned to a SIT or ET group (n= 8 each) and performed six training sessions over 14 days. Each session consisted of either four to six repeats of 30 s ‘all out’ cycling at ∼250% with 4 min recovery (SIT) or 90–120 min continuous cycling at ∼65% (ET). Training time commitment over 2 weeks was ∼2.5 h for SIT and ∼10.5 h for ET, and total training volume was ∼90% lower for SIT versus ET (∼630 versus∼6500 kJ). Training decreased the time required to complete 50 and 750 kJ cycling time trials, with no difference between groups (main effects, P≤ 0.05). Biopsy samples obtained before and after training revealed similar increases in muscle oxidative capacity, as reflected by the maximal activity of cytochrome c oxidase (COX) and COX subunits II and IV protein content (main effects, P≤ 0.05), but COX II and IV mRNAs were unchanged. Training‐induced increases in muscle buffering capacity and glycogen content were also similar between groups (main effects, P≤ 0.05). Given the large difference in training volume, these data demonstrate that SIT is a time‐efficient strategy to induce rapid adaptations in skeletal muscle and exercise performance that are comparable to ET in young active men.
Immunohistochemical analysis of B-cell lymphoma -2 in pleomorphic adenoma and mucoepidermoid carcinoma

Background: Salivary gland tumors form a major area in the field of oral pathology. B-cell lymphoma -2 (Bcl-2) is an anti-apoptotic gene with up-regulation in various neoplasms. The aim of the present case-control study was to comparatively investigate the expression of Bcl-2 protein in pleomorphic adenoma (PA) and mucoepidermoid carcinoma (MEC) and assess its potential diagnostic role in differentiating these tumors. Materials and Methods: A total of 28 cases (18 specimens of PA [control] and 10 blocks of MEC [case]) were selected for analysis by streptavidin-biotin peroxidase method with antibody against Bcl-2. The percentage of positive cells was calculated from a minimum of 1000 neoplastic cells and H-score was identified (% positive cells × intensity of staining). Data were analyzed using two-way ANOVA, t-test, Spearman, Chi-square and Fisher tests (α = 0.05). Results: bcl-2 expression was shown in 13 cases (71%) of PA and 3 cases (30%) of MEC. In addition, four cases of PA showed strong staining. There was a significant difference between the expression intensity of Bcl-2 in the two tumors (P = 0.048) according to ANOVA. No correlation was observed between Bcl-2 expression with the size and location of tumors (P > 0.05). Conclusion: Bcl-2 expression might be used for differentiating these tumors. Bcl-2 protein was overexpressed in PA compared with MEC. Hence, it seems that unlike what was observed in PA, Bcl-2 probably does not participate in the pathogenesis of MEC.
Diagnostic Value of the CD103+CD4+/CD4+ Ratio to Differentiate Sarcoidosis from Other Causes of Lymphocytic Alveolitis

Background: The CD103 integrin is present on CD4+ lymphocytes of the bronchial mucosa, but not on peripheral blood CD4+ lymphocytes. It has been hypothesized that CD4+ lymphocytes in pulmonary sarcoidosis originate from redistribution from the peripheral blood to the lung, and therefore do not bear the CD103 integrin. Some data suggest that a low CD103+ percentage among bronchoalveolar lavage fluid (BALF) CD4+ lymphocytes discriminates between sarcoidosis and other diagnoses. Objective: To determine the diagnostic value of BALF CD103+ to identify sarcoidosis among other causes of alveolar lymphocytosis in a large retrospective case series. Methods: Among 391 consecutive bronchoalveolar lavages performed at our institution and analyzed by flow cytometry, we identified 207 cases, which were grouped into nine diagnostic categories: sarcoidosis, tuberculosis, non-tuberculous infections, hypersensitivity pneumonitis, non-specific interstitial pneumonia, organizing pneumonia, drug-induced lung diseases, other interstitial lung diseases (ILDs), and other diagnoses. To assess the discriminative value of the CD103+CD4+/CD4+ ratio to distinguish sarcoidosis from other entities, areas under ROC curves (AUC) were calculated. Results: Sarcoidosis patients (n = 53) had significantly lower CD103+CD4+/CD4+ ratios than patients in other diagnostic categories. The AUC was 62% for sarcoidosis compared to all other diagnoses, and 69% for sarcoidosis compared to other ILDs. When combining CD103+CD4+/CD4+ and CD4+/CD8+ ratios, the AUC increased to 76 and 78%, respectively. When applying previously published cut-offs to our population, the AUC varied between 54 and 73%. Conclusions: The CD103+CD4+/CD4+ ratio does not accurately discriminate between sarcoidosis and other causes of lymphocytic alveolitis, neither alone nor in combination with the CD4+/CD8+ ratio, and is not a powerful marker for the diagnosis of sarcoidosis.
Nonclinical and Clinical Enterococcus faecium Strains, but Not Enterococcus faecalis Strains, Have Distinct Structural and Functional Genomic Features

ABSTRACT Certain strains of Enterococcus faecium and Enterococcus faecalis contribute beneficially to animal health and food production, while others are associated with nosocomial infections. To determine whether there are structural and functional genomic features that are distinct between nonclinical (NC) and clinical (CL) strains of those species, we analyzed the genomes of 31 E. faecium and 38 E. faecalis strains. Hierarchical clustering of 7,017 orthologs found in the E. faecium pangenome revealed that NC strains clustered into two clades and are distinct from CL strains. NC E. faecium genomes are significantly smaller than CL genomes, and this difference was partly explained by significantly fewer mobile genetic elements (ME), virulence factors (VF), and antibiotic resistance (AR) genes. E. faecium ortholog comparisons identified 68 and 153 genes that are enriched for NC and CL strains, respectively. Proximity analysis showed that CL-enriched loci, and not NC-enriched loci, are more frequently colocalized on the genome with ME. In CL genomes, AR genes are also colocalized with ME, and VF are more frequently associated with CL-enriched loci. Genes in 23 functional groups are also differentially enriched between NC and CL E. faecium genomes. In contrast, differences were not observed between NC and CL E. faecalis genomes despite their having larger genomes than E. faecium. Our findings show that unlike E. faecalis, NC and CL E. faecium strains are equipped with distinct structural and functional genomic features indicative of adaptation to different environments.
Enterobacterial repetitive intergenic consensus sequences and the PCR to generate fingerprints of genomic DNAs from Vibrio cholerae O1, O139, and non-O1 strains

Enterobacterial repetitive intergenic consensus (ERIC) sequence polymorphism was studied in Vibrio Cholerae strains isolated before and after the cholera epidemic in Brazil (in 1991), along with epidemic strains from Peru, Mexico, and India, by PCR. A total of 17 fingerprint patterns (FPs) were detected in the V. cholerae strains examined; 96.7% of the toxigenic V. cholerae O1 strains and 100% of the O139 serogroup strains were found to belong to the same FP group comprising four fragments (FP1). The nontoxigenic V. cholerae O1 also yielded four fragments but constituted a different FP group (FP2). A total of 15 different patterns were observed among the V. cholerae non-O1 strains. Two patterns were observed most frequently for V. cholerae non-01 strains, 25% of which have FP3, with five fragments, and 16.7% of which have FP4, with two fragments. Three fragments, 1.75, 0.79, and 0.5 kb, were found to be common to both toxigenic and nontoxigenic V. cholerae O1 strains as well as to group FP3, containing V. cholerae non-O1 strains. Two fragments of group FP3, 1.3 and 1.0 kb, were present in FP1 and FP2 respectively. The 0.5-kb fragment was common to all strains and serogroups of V. cholerae analyzed. It is concluded from the results of this study, based on DNA FPs of environmental isolates, that it is possible to detect an emerging virulent strain in a cholera-endemic region. ERIC-PCR constitutes a powerful tool for determination of the virulence potential of V. cholerae O1 strains isolated in surveillance programs and for molecular epidemiological investigations.
Vitamin D status in healthy Indians aged 50 years and above.

INTRODUCTION There is widespread prevalence of vitamin D deficiency from new-born to infancy, childhood and adult male and females (non-pregnant, pregnant and lactating). However, there is limited information of the vitamin D status in elderly Indians. MATERIAL AND METHODS The study was carried in 1346 healthy subjects more than 50 years of age residing in Delhi, India. These subjects, who were divided in two groups: Group-1 (50-< 65 years) and Group-2 (> or = 65 years), underwent anthropometric, biochemical and hormonal evaluation for vitamin D status Bone mineral density was measured by dual X-ray absorptiometry. RESULTS There were 643 males and 703 females, with a mean age of 58.0 +/- 9.5 years (range 50-84 years). Vitamin D deficiency [VDD, serum 25(OH)D levels < 20 ng/ml) was present in 1228 (91.2%) and Vitamin D insufficiency [VDI, serum 25(OH)D levels 20-< 30 ng/ml] in 92 (6.8%). There was no significant difference in prevalence of either VDD or VDI between two age groups and sexes. Serum 25(OH)D levels were negatively correlated with PTH levels (r -0.027, p <0.00001) and BMI (r -0.128, p 0.05). Prevalence of secondary hyperparathyroidism increased from 14.1% to 43.1% from VDI to severe VDD. PTH levels started rising at vitamin D level < 30 ng/ml. However, more than 50% of subjects with severe VDD had PTH levels within normal range. High prevalence of osteopenia (50.2%) and osteoporosis (31.2%) was observed in this population. CONCLUSION Hypovitaminosis D is universal above the age of 50 years in north India. Absence of a PTH response was observed in more than 50% of individuals with VDD, the cause of which merits further evaluation. Normal bone mass was observed in only 18.6% of study subjects.