Inhibition of Virus Attachment to CD4+ Target Cells Is a Major Mechanism of T Cell Line–adapted HIV-1 Neutralization

Antibody-mediated neutralization of human immunodeficiency virus type–1 (HIV-1) is thought to function by at least two distinct mechanisms: inhibition of virus–receptor binding, and interference with events after binding, such as virus–cell membrane fusion. Here we show, by the use of a novel virus–cell binding assay, that soluble CD4 and monoclonal antibodies to all confirmed glycoprotein (gp)120 neutralizing epitopes, including the CD4 binding site and the V2 and V3 loops, inhibit the adsorption of two T cell line–adapted HIV-1 viruses to CD4⁺ cells. A correlation between the inhibition of virus binding and virus neutralization was observed for soluble CD4 and all anti-gp120 antibodies, indicating that this is a major mechanism of HIV neutralization. By contrast, antibodies specific for regions of gp120 other than the CD4 binding site showed little or no inhibition of either soluble gp120 binding to CD4⁺ cells or soluble CD4 binding to HIV-infected cells, implying that this effect is specific to the virion–cell interaction. However, inhibition of HIV-1 attachment to cells is not a universal mechanism of neutralization, since an anti-gp41 antibody did not inhibit virus–cell binding at neutralizing concentrations, implying activity after virus–cell binding.     

Non-invasive prediction of esophageal varices by stiffness and platelet in non-alcoholic fatty liver disease cirrhosis

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Oncological outcomes of IBD-associated versus sporadic colorectal cancer in modern era: a matched case-control study

Aim

Inflammatory bowel diseases (IBD) are associated with an increased risk for colorectal cancer (CRC). However and despite significant advances in the management of IBD and CRC, the prognosis of IBD-related CRC (IBD-CRC) remains controversial. The aim of the present case-control study was to compare the prognosis of IBD-CRC to sporadic CRC.

Methods

Consecutive patients operated for IBD-CRC from 2004 to 2014 were recruited and matched with sporadic CRC (ratio 3:1) from the same center. Matching was performed on gender, tumor stage, and location and period of surgery. Endpoints were postoperative morbidity (Dindo-Clavien III-V), quality of surgery, and long-term oncological outcomes.

Results

Among 1498 CRC patients operated during the study period, 21 patients were identified with IBD-CRC and matched to 63 patients with sporadic CRC (S-CRC). Patients with IBD-CRC were significantly younger (p?<?0.001), had multifocal lesions more frequently (p?=?0.04), and undergone abdominoperineal excision and coloproctectomy more often (p?=?0.001). Postoperative morbidity was not significantly different between the two groups (25 vs. 14%; p?=?0.309), as well as the rate of R0 resection (86 vs. 95%; p?=?0.162). Five-year disease-free and overall survival were 71 and 81% in patients with IBD-CRC and 69% (p?=?0.801) and 78% (p?=?0.845) in those with S-CRC, respectively.

Conclusion

In a case-control study of patients operated for CRC within the last decade, the prognosis of cancer associated with IBD is similar to sporadic cancer.

     

Bioresorbable vascular scaffold to treat in‐stent restenosis: Single‐center experience

Aims

The management of patients with in‐stent restenosis (ISR) is still a major clinical challenge even in the era of drug‐eluting stents (DES). Recent studies have demonstrated acceptable clinical outcomes for the everolimus‐eluting bioresorbable vascular scaffold (BVS) ABSORB? in patients with stable coronary artery disease but data are scarce on its use in patients with ISR. We report the long‐term results of our preliminary experience with this novel approach at our institution.

Methods and Results

We investigated the safety and efficacy of BVS implantation to treat ISR. 34 consecutive patients (37 lesions) underwent PCI for ISR with BVS implantation between May 2013 and June 2015 at our institution and were included in the current analysis. Follow‐up was available in 91.9% of the patients. Mean follow‐up period was 801.9 ± 179 days. One patient had definite scaffold thrombosis (ScT) 2 months after stent implantation which was treated with DES. Five patients (six lesions) experienced target lesion revascularization (TLR). The composite endpoint rate of TLR, ScT, myocardial infarction, and death occured in 6/37 lesions at follow‐up (16.2%).

Conclusions

These real‐world data using BVS in patients with ISR demonstrates that ISR treatment with ABSORB? BVS is feasible but could have slightly higher target lesion failure rates as compared to DES. This proof of concept could be hypothesis‐generating for larger randomized controlled studies.

     

Escherichia coli strains from pregnant women and neonates: intraspecies genetic distribution and prevalence of virulence factors

To determine the extent to which the vagina, endocervix, and amniotic fluid screen the Escherichia coli strains responsible for neonatal infections, we studied the genetic relationships among 105 E. coli strains isolated from all of the ecosystems involved in this infectious process. Twenty-four strains were isolated from the intestinal flora, and 25 strains were isolated from the vaginas of pregnant women. Twenty-seven strains were isolated from the amniotic fluid, blood, and cerebrospinal fluid (CSF) of infected neonates. The intraspecies genetic characteristics of all of the isolates were determined by random amplified polymorphic DNA (RAPD) analysis, PCR ECOR (E. coli reference) grouping, and PCR virulence genotyping. A correlation was found between the intraspecies distributions of the strains in the A, B1, B2, and D ECOR groups and in the two major RAPD groups (I and II). Nevertheless, the distribution of the E. coli strains in the RAPD groups according to their anatomical origins was more significant than their distribution in the ECOR groups. This may be explained by the existence of an E. coli subpopulation, defined by the RAPD I group, within the ECOR B2 group. This RAPD I group presents a major risk for neonates: 75% of the strains isolated from patients with meningitis and 100% of the strains isolated from patients with bacteremia were in this group. The vagina and the amniotic fluid are two barriers that favor colonization by highly infectious strains. Indeed, only 17% of fecal strains belonged to the RAPD I group, whereas 52% of vaginal strains and 67% of amniotic fluid strains belonged to this subpopulation. The ibeA and iucC genes were significantly associated with CSF strains, whereas the hly and sfa/foc genes were more frequent in blood strains. These findings could serve as a basis for developing tools to recognize vaginal strains, which present a high risk for neonates, for use in prophylaxis programs.     

Chemistry of the Fe2O3/BiFeO3 Interface in BiFeO3 Thin Film Heterostructures

We investigate the interfacial chemistry of secondary Fe₂O₃ phases formed in a BiFeO₃ (BFO) layer in BFO/ La_0.67Sr_0.33MnO₃ (LSMO)/SrTiO₃ (STO) heterostructures. A combination of high-resolution spherical aberration corrected scanning TEM and spectroscopy results, reveals that specific chemical and crystallographic similarities between Fe₂O₃ and BFO, enable the BFO layer to form a facile host for Fe₂O₃.     

Urotensin I-CRF-Urocortins: A mermaid’s tail

From the individual perspective of the two authors who were long-time colleagues of Karl Lederis at the University of Calgary, the events and personal interactions are described, that are relevant to the discovery of Urotensin I (UI) in the Lederis laboratory, along with the concurrent discovery of Urotensin II (UII) in the Bern laboratory and corticotropin-releasing factor (CRF/CRH) in the Vale laboratory. The fortuitous sabbatical experiences that put Professors Lederis and Bern on the track of the Urotensins, along with the essential isolation paradigm that resulted in the complete sequencing and synthesis of UI and UII are summarized. The chance interaction between Drs. Vale and Lederis who, prior to the publications of the sequences of UI and CRF, realized the sequence commonalities of these peptides with the vasoactive frog peptide, sauvagine, is outlined. Further, the relationship between the pharmacological studies done with UI in the Calgary laboratory and the more recent understanding of the biology and receptor pharmacology for the entire Urotensin I-CRF-Urocortin peptide family is dealt with. The value of a comparative endocrinology approach to understanding hormone action is emphasized, along with a projection to the future, based on new hypotheses that can be generated by unexplained data already in the literature. Based on the previously described pharmacology of the UI-CRF-Urocortin peptides in a number of target tissues, it is suggested that the use of current molecular approaches can be integrated with a ‘classical’ pharmacological approach to generate new insights about the UI-CRF-Urocortin hormone family.     

Drug-related problems in hospitalized patients with HIV infection.

PURPOSE: The type and number of drug-related problems that commonly occur in hospitalized patients with HIV were studied. METHODS: The medical records of HIV-infected patients who were receiving antiretroviral therapy at the time of hospital admission between January 1, 2005, and August 31, 2006, were reviewed. Patients age 18 years or older who had received at least one dose of an antiretroviral for an HIV-related indication during their hospitalization were included in the study. Patients' medical records were evaluated to identify drug-related problems and adverse drug events secondary to antiretroviral therapy. RESULTS: Eighty-three patients were eligible for study inclusion. A total of 176 drug-related problems were identified. The most common drug-related problem identified among medication orders reviewed was inappropriate dosing. Of the 251 orders for antiretroviral agents, 57 drugs were inappropriately dosed. The most common drug-related problems among patients were drug-drug interactions and incomplete antiretroviral regimens. There was no significant difference in the mean length of stay between patients with or without drug-related problems. Admission by physicians who were not infectious diseases specialists was an independent risk factor for having at least one drug-related problem during hospitalization (odds ratio, 3.83; 95% confidence interval, 1.08-13.54). CONCLUSION: A majority of HIV-infected patients at one institution had at least one drug-related problem at hospital admission. The most common problem observed among the medication orders reviewed was inappropriate dosing. The most common drug-related problems observed among patients were drug-drug interactions and incomplete antiretroviral regimens.