Mycobacterium tuberculosis heat-shock protein 70 impairs maturation of dendritic cells from bone marrow precursors, induces interleukin-10 production and inhibits T-cell proliferation in vitro

In different inflammatory disease models, heat-shock proteins (hsp) and hsp-derived peptides have been demonstrated to possess anti-inflammatory properties. While some studies have shown that hsp can directly interact with antigen-presenting cells, others report that bacterial hsp can induce specific T cells with regulatory phenotypes. Effective characterization of the immunomodulatory effects of hsp 70, however, has historically been confounded by lipopolysaccharide (LPS) contamination. In this study, we compared the effects of LPS-free Mycobacterial tuberculosis hsp 70 (TBhsp70) and its possible contaminants on dendritic cells (DC). We demonstrate herein that LPS-free TBhsp70 inhibits murine DC maturation in vitro, while LPS-contaminated TBhsp70 induces DC maturation. Mock recombinant preparations have no effect. In contrast to LPS, TBhsp70 does not induce tumour necrosis factor-alpha production by DC, but interleukin-10. In vivo, only LPS-contaminated TBhsp70 induces up-regulation of CD86 in splenic mature DC. Finally, TBhsp70 inhibited phytohaemagglutinin-induced T-cell proliferation. Our results support the hypothesis that TBhsp70 does not have inflammatory potential, but rather has immunosuppressive properties.     

Interferon-alpha and ribavirin resistance of Huh7 cells transfected with HCV subgenomic replicon

To model HCV resistance to a treatment with interferon-alpha (IFN-alpha) and ribavirin, Huh7 cells, bearing HCV subgenomic replicons, were treated with these compounds for several weeks. Analysis of the cell clones, which were able to support replication of HCV RNA in the presence of high concentrations of these antivirals, demonstrated that the observed resistance was due to changes in the host cell phenotype but not to the emergence of resistant variants of the replicon. No changes in the type I IFN receptor mRNA levels or sequences were found in IFN-treated cells suggesting that the observed resistance of replicon-containing cells to IFN-alpha was caused by modifications of some other cellular factors. The resistance of cells to high concentrations of ribavirin was due to a single point mutation in the NS5A gene of the HCV replicon, and was not associated with a defect in a ribavirin uptake. This mutation, however, did not change the sensitivity of the replicon itself to this antiviral.     

Budget impact analysis of the adoption of new hypertension guidelines in Colombia

Background

Hypertension represents a high burden of disease in different healthcare systems. Recent guideline published in 2017 by the American Heart Association and the American College of Cardiology has generated a debate between clinicians and policymakers due to the lowering of diagnosis threshold and the subsequent increase of the prevalence and healthcare costs. No empirical research exists addressing the question about the pressure on healthcare costs generated by new standards. This study aims to quantify the impact on the hypertension diagnosis and treatment costs for healthcare system using the new hypertension guideline.

Methods

We conducted a budget impact analysis from a Colombianhealthcare payer’s perspective with a 3-year time horizon (2018–2020), in which we estimated the difference in total medical care costs between previous hypertension cut-off points (140/90 mmHg) and new guideline cut-off points (130/80 mmHg).

Results

Our results show that the impact of the adoption of the new hypertension guideline would represent a decrease close to 22% in total annual high blood pressure costs in Colombia. This reduction is mainly driven by a lower number of cardiovascular complications. It is worth noting that these results should be taken with caution due to local available data.

Conclusions

A high-middle income country such as Colombia should carry out an exhaustive revision of the recommendations of the new hypertension guideline, due to its high probability of saving medical treatment costs for the healthcare system.

     

Health care service utilization of documented and undocumented hired farmworkers in the U.S.

This article analyzes issues related to U.S. hired farmworkers’ utilization of health care services and their specific choices among health care provider and health bill payment method options. Using data from the National Agricultural Workers Surveys for the years 2000–2012, this article employs propensity score matching and probit estimation techniques to examine the health care utilization of hired farmworkers. This study’s results indicate that undocumented hired farmworkers are 10.7 and 3% less likely to use U.S. and foreign health care, respectively, compared to documented farmworkers. Health insurance is found to significantly increase hired farmworkers’ use of U.S. health care by 22.3%. Notably, compared to their documented working peers, undocumented workers are much less likely to patronize private clinics. They are even less likely to rely on migrant health centers even when these providers are their most viable sources of health care service.     

Knowledge of appropriate acetaminophen use: A survey of college-age women

Objectives

To evaluate college-age women’s knowledge of appropriate doses and potential toxicities of acetaminophen, competency in interpreting Drug Facts label dosing information, and ability to recognize products containing acetaminophen.

Anomalous coronary artery causing transmural ischaemia and ventricular tachycardia in a high school athlete

A previously asymptomatic 15-year-old boy was treated at our institution after an episode of chest pain, palpitation, and syncope while playing in a high school soccer game. The patient's resting electrocardiogram was normal. A transthoracic echocardiogram showed an anomalous left main coronary artery originating from the right sinus of Valsalva. Contrast-enhanced multidetector computed tomography demonstrated clearly that the anomalous vessel coursed between the aorta and the pulmonary trunk (interarterial subtype). Treadmill testing registered several nonsustained polymorphic ventricular tachycardias and transmural myocardial ischaemia in the early recovery phase (ST-elevation up to 5mm in CM5 and V2 leads). The patient underwent bypass grafting. One year later, he remains asymptomatic, and new treadmill tests have been normal. In this patient, severe transmural myocardial ischaemia was detected, possibly due to collapse or vasospasm of the anomalous vessel, triggering life-threatening ventricular arrhythmias.     

Evaluation of ceftobiprole medocaril against Enterococcus faecalis in a mouse peritonitis model

OBJECTIVES: Ceftobiprole is a novel broad-spectrum cephalosporin with good in vitro activity against methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. The objective of this study was to assess the in vivo activity of ceftobiprole against four strains of E. faecalis, including beta-lactamase- producing (Bla+) and vancomycin-resistant strains. METHODS: Mice were infected intraperitoneally with strains of E. faecalis: (i) the Bla+ strain HH22; (ii) two vancomycin-resistant strains (TX2484 and V583); and (iii) OG1RF (a laboratory strain), using 10 x the LD50 for each strain. Ceftobiprole doses of 25, 12.5 and 6.25 mg/kg (single doses) and ampicillin 50, 25, 12.5 and 6.25 mg/kg (single and double doses) were administered subcutaneously immediately after bacterial challenge and mice were monitored for 96 h. RESULTS: All four E. faecalis had ceftobiprole MICs 100 mg/kg, whereas ceftobiprole was protective (PD50 of 2 mg/kg). Ceftobiprole PD50s for vancomycin-resistant isolates TX2484 and V583 were 7.7 and 5.2 mg/kg, respectively, similar to those of single dose ampicillin (12.5 and 16.4 mg/kg, respectively). For OG1RF, both ampicillin and ceftobiprole protected all mice at doses of 25 and 12.5 mg/kg, respectively, with a PD50 of 4.2 and 8 mg/kg for ceftobiprole and ampicillin, respectively. CONCLUSIONS: Ceftobiprole had comparable in vivo activity to that of ampicillin against vancomycin-resistant and ampicillin-susceptible strains of E. faecalis in the mouse peritonitis model. Ceftobiprole was superior in vivo to ampicillin against the Bla+ strain HH22. Our data support the further study of ceftobiprole as a therapeutic agent in humans infected with E. faecalis.