High Stroke Volume Para-aortic Counterpulsation Device versus Centrifugal Pump in Cardiogenic Shock: Experimental Study

p < 0.001), the tension time index (712 ± 381 versus 1333 ± 694, p < 0.01), and the double product (5629 ± 2574 versus 7440 ± 3294, p < 0.01) were significantly lower during assistance with the PACD than with the CBP. It was concluded that PACD is at least as effective as CBP for restoring hemodynamic status during acute experimental cardiogenic shock. Moreover, the PACD unloads the left ventricle more effectively than CBP, making it suitable for left ventricular mechanical support in cases with reversible myocardial damage.     

ProbCons: Probabilistic consistency-based multiple sequence alignment

To study gene evolution across a wide range of organisms, biologists need accurate tools for multiple sequence alignment of protein families. Obtaining accurate alignments, however, is a difficult computational problem because of not only the high computational cost but also the lack of proper objective functions for measuring alignment quality. In this paper, we introduce probabilistic consistency, a novel scoring function for multiple sequence comparisons. We present ProbCons, a practical tool for progressive protein multiple sequence alignment based on probabilistic consistency, and evaluate its performance on several standard alignment benchmark data sets. On the BAliBASE, SABmark, and PREFAB benchmark alignment databases, ProbCons achieves statistically significant improvement over other leading methods while maintaining practical speed. ProbCons is publicly available as a Web resource.     

Distribution and intensity of constraint in mammalian genomic sequence

Comparisons of orthologous genomic DNA sequences can be used to characterize regions that have been subject to purifying selection and are enriched for functional elements. We here present the results of such an analysis on an alignment of sequences from 29 mammalian species. The alignment captures approximately 3.9 neutral substitutions per site and spans approximately 1.9 Mbp of the human genome. We identify constrained elements from 3 bp to over 1 kbp in length, covering approximately 5.5% of the human locus. Our estimate for the total amount of nonexonic constraint experienced by this locus is roughly twice that for exonic constraint. Constrained elements tend to cluster, and we identify large constrained regions that correspond well with known functional elements. While constraint density inversely correlates with mobile element density, we also show the presence of unambiguously constrained elements overlapping mammalian ancestral repeats. In addition, we describe a number of elements in this region that have undergone intense purifying selection throughout mammalian evolution, and we show that these important elements are more numerous than previously thought. These results were obtained with Genomic Evolutionary Rate Profiling (GERP), a statistically rigorous and biologically transparent framework for constrained element identification. GERP identifies regions at high resolution that exhibit nucleotide substitution deficits, and measures these deficits as "rejected substitutions". Rejected substitutions reflect the intensity of past purifying selection and are used to rank and characterize constrained elements. We anticipate that GERP and the types of analyses it facilitates will provide further insights and improved annotation for the human genome as mammalian genome sequence data become richer.     

Growth Delay in Inflammatory Bowel Diseases: The Importance of Surgery

Digestive Diseases and Sciences -     

Increased HLA-G Expression in Tissue-Infiltrating Cells in Inflammatory Bowel Diseases

Background

Since HLA-G is an immune checkpoint molecule and since Crohn’s disease (CD) and ulcerative colitis (UC) exhibit deregulated immune-mediated mechanisms, we aimed to evaluate intestinal HLA-G expression and soluble HLA-G (sHLA-G) levels in CD/UC patients stratified according to the CD phenotype/localization and UC extension.

Methods

HLA-G tissue expression was assessed by immunohistochemistry in biopsies collected from 151 patients (90 CD, 61 UC) and in surgical resection specimens (28 CD, 12 UC). Surgical material from 24 healthy controls was also assessed. Plasma sHLA-G levels (97 CD, 81 UC, and 120 controls) were evaluated using ELISA.

Results

HLA-G expression was similarly observed in the intestinal epithelial cells of control and CD/UC specimens. However, in biopsies, the plasma cells/lymphocytes infiltrating the lamina propria in CD/UC presented (1) increased HLA-G expression compared to controls (P?<?0.0001), (2) greater cell staining in UC cells than in CD cells irrespective of disease extent (P?=?0.0011), and (3) an increased number of infiltrating cells in the inflammatory CD phenotype compared to that in the stenosing and fistulizing phenotypes (P?=?0.0407). In surgical specimens, CD/UC patients exhibited higher infiltrating cell HLA-G expression in lesion areas than in margins. sHLA-G levels were higher in UC/CD patients (P?<?0.0001) than in controls, but no difference was observed between diseases.

Conclusions

Increased infiltrating cell HLA-G expression associated with increased sHLA-G levels in CD/UC patients may reflect ongoing host strategies to suppress chronic inflammation.

     

Dynamic hyperinflation and tolerance to interval exercise in patients with advanced COPD.

Dynamic hyperinflation (DH) contributes importantly to the limitation of constant-load exercise (CLE) in patients with chronic obstructive pulmonary disease (COPD). However, its role in the limitation of interval exercise (IE) remains to be explored. The change (Delta) in inspiratory capacity (IC) was measured to reflect changes in DH in 27 COPD patients (forced expiratory volume in one second mean+/-SEM % predicted: 40+/-3) at the end of a symptom-limited CLE test at 80% of peak work capacity (WRmax) and an IE test at 100% WRmax (30 s of work, alternated with 30 s of unloaded pedalling). At the limit of tolerance in both IE and CLE, patients exhibited similar DH (DeltaIC: 0.39+/-0.05 L and 0.45+/-0.05 L, respectively). However, exercise endurance time (t end) for IE (32.7+/-3.0 min) was significantly greater than for CLE (10.3+/-1.6 min). The IE t end correlated with resting IC, expressed as % pred normal. At 30 and 90% of total IE t end, DeltaIC (0.43+/-0.06 and 0.39+/-0.05 L, respectively) and minute ventilation (31.1+/-1.6 and 32.7+/-2.2 L.min(-1), respectively) were not significantly different. Resting hyperinflation helps to explain the limitation of interval exercise. Implementation of interval exercise for rehabilitation should provide important clinical benefits because it prolongs exercise endurance time and allows sustaining higher stable ventilation.     

Acute coronary and peripheral arterial thrombosis following percutaneous coronary intervention in a patient with previously undiagnosed inherited thrombophilia

Following pretreatment with ticlopidine 250 mg bid for three days, a 40-year-old man underwent successful angioplasty and stenting of the proximal left anterior descending coronary artery and balloon dilation of the midcircumflex coronary artery without stenting. He subsequently developed acute coronary thromboses at both arterial sites and cardiogenic shock. The patient survived after an additional percutaneous coronary intervention (PCI) and intra-aortic balloon pump assistance. This was followed by peripheral arterial thrombosis requiring repeated therapeutic interventions. Laboratory tests for thrombophilia revealed the presence of a G20210A prothrombin gene mutation. Two years later the patient remained free of angina and claudication, and underwent an unremarkable maximum exercise treadmill test. This is the first reported case of acute, multiple coronary and peripheral arterial thrombosis following PCI in a patient with previously unsuspected inherited thrombophilia. Inherited thrombophilia should be considered as a possible cause of arterial thrombosis following PCI.     

H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

This study investigated the role of H₁ and H₂ receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H₂ receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H₁ receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H₁ receptor, but not H₂, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.     

The crowding effect in Ancylostoma ceylanicum: density-dependent effects on an experimental model of infection

This study compared the course of Ancylostoma ceylanicum infection in hamsters infected with different inocula and the consequences for the host and helminth populations. The average of adult worms recovered, according to the number of third stage larva used, were 28.0, 24.8, 24.6, and 24.8 % to inocula size of 25 L3, 75 L3, 125 L3, and 250 L3, respectively. The size of the inoculum did not affect the establishment, survival, or fecundity of adult helminths. Reductions in the red blood cell and hemoglobin levels in the infected group were inversely proportional to the number of white blood cells. Moreover, differential cell counting revealed a positive correlation between the worm load and leucocyte numbers. The humoral response against excretion-secretion antigens was more robust and sensitive compared with the response against crude extract, with no direct linear correlation with the number of worms. The effect of the population density was more evident in females.