Production of the subdomains of the Plasmodium falciparum apical membrane antigen 1 ectodomain and analysis of the immune response

The apical membrane antigen 1 of Plasmodium falciparum is one of the leading candidate antigens being developed as a vaccine to prevent malaria. This merozoite transmembrane protein has an ectodomain that can be divided into three subdomains (D I, D II, and D III). We have previously expressed a major portion of this ectodomain and have shown that it can induce antibodies that prevent merozoite invasion into red blood cells in an in vitro growth and invasion assay. To analyze the antibody responses directed against the individual subdomains, we constructed six different genes that express each of the domains separately (D I, D II, or D III) or in combination with another domain (D I+II, D II+III, or D I+III). These proteins were purified and used to immunize rabbits to raise construct-specific antibodies. We demonstrated that D I+II induced a significant amount of the growth-inhibitory antibodies active in the growth and invasion assay.     

Efficacy of virosome hepatitis A vaccine in young children in Nicaragua: randomized placebo-controlled trial

Immunization of young children could control hepatitis A virus (HAV) infection, but the efficacy of hepatitis A vaccines in early childhood is unknown. In a randomized, double-blind trial of a single dose of a virosome-formulated, aluminum-free inactivated HAV vaccine in Nicaragua, 274 children (age range, 1.5-6 years) received vaccine or placebo injections; 239 children seronegative for hepatitis A were included in the primary efficacy analysis. HAV infection documented by immunoglobulin M antibodies was the primary end point. Among children seronegative for hepatitis A, infection was diagnosed in 4 children in the vaccine group and 22 children in the placebo group (protective efficacy, 84.6%; 95% confidence interval, 54.7%-96.1%). All infections in children in the vaccine group occurred within 6 weeks. After 6 weeks, protective efficacy was 100% (79.8%-100%). In children in the placebo group, the incidence of HAV infection was 17.6 and that of icteric illness was 1.6 cases/100 person-years. Adverse effects were rare in both children in the vaccine group and children in the placebo group. A single dose of a hepatitis A virosome vaccine is safe and protects young children against HAV infection.     

A New “Silver-Bullet” to treat caries in children – Nano Silver Fluoride: A randomised clinical trial

Background

Untreated dental caries in children remains a public health challenge in poor communities.

Objectives

This prospective controlled clinical trial investigated the effectiveness of a new anti-caries agent, Nano Silver Fluoride (NSF), applied once a year to arrest caries in children.

Methods

One hundred thirty decayed primary teeth were randomly divided into two groups: NSF as the experimental agent and water as the control group. Teeth were clinically diagnosed and treated by one masked examiner and followed up at seven days and five and 12 months by another calibrated examiner who was blinded to the type of treatment. The criteria of the ICDAS II were followed to determine the activity of lesion and the diagnosis of caries. The Pearson's chi-square test was used to compare the groups during different follow-up exams.

Results

At seven days, 81% of teeth in the NSF group exhibited arrested caries, whereas in controls, no teeth had arrested decay (p < 0.001) [PF, prevented fraction = 81%]. After five months, the NSF group had 72.7% with arrested decay, and the control group had 27.4% (p < 0.001) [PF = 62.5%]. At 12 months, 66.7% of the lesions treated with NSF were still arrested, while the control group had 34.7% remaining arrested (p = 0.003) [PF = 50%]. The number need to treat (NNT) at five months was two, and at 12 months, the number was three.Clinical Signi?cance: The NSF formulation is effective to arrest active dentine caries and not stain teeth.

Conclusions

NSF was demonstrated to be effective in arresting caries in children in poor communities.     

Effects of obesity on burn resuscitation

The effects of obesity on resuscitation after severe burn are not well understood. Formulas to calculate 24-h resuscitation volumes incorporate body weight, which in obese patients often leads to excessive fluid administration and potential complications such as pulmonary edema, extremity or abdominal compartment syndrome, and longer mechanical ventilation. We evaluated the impact of obesity on 24-h fluid resuscitation after severe burn using a cohort of 145 adults admitted to the burn ICU from January 2014 to March 2017 with >20% total body surface area burns. Patients were divided into four groups based on body mass index: normal weight (index of <25), overweight (25–29.9), obese (30–39.9), and morbidly obese (>40). Median total body surface area burn was 39.4% (interquartile range: 23.5%–49.5%). Patients were 74.5% male and demographics and injury characteristics were similar across groups. Resuscitation volumes exceeded the predicted Parkland formula volume in the normal and overweight groups but were less than predicted in the obese and morbidly obese categories (p < 0.001). No difference was found in 24-h urine output between groups (p = 0.08). Increasing body mass index was not associated with increased use of renal replacement therapy. Only total body surface area burned, and age were independent predictors of hospital mortality (p < 0.001). We conclude that using body weight to calculate resuscitation in obese patients results in a predicted fluid volume that is higher than the volume actually given, which can lead to over-resuscitation if rates are not titrated regularly to address fluid responsiveness.     

Plasminogen activator inhibitor type 1 serum levels and 4G/5G gene polymorphism in morbidly obese Hispanic patients with non-alcoholic fatty liver disease

Background. The plasminogen activator inhibitor type-1 (PAI-1) has been implicated in the regulation of fibrinolysis and extracellular matrix components. The single base pair guanine insertion/deletion polymorphism (4G/5G) within the promoter region of the PAI-1 gene influences PAI-1 synthesis and may modulate hepatic fibrogenesis.Aim. To evaluate the influence of PAI-1 serum levels and 4G/5G polymorphism on the risk of liver fibrosis associated to non-alcoholic fatty liver disease (NAFLD) in morbidly obese patients.Material and methods. Case-control study of 50 obese patients undergoing bariatric surgery and 71 non-obese subjects matched by age and sex. Anthropometric and biochemical measurements were performed, including PAI-1 serum levels. Genomic DNA was obtained to assess the presence of 4G/5G polymorphism.Results. BMI, insulinemia, triglycerides, HOMA-IR, hypertension and diabetes were significantly higher in obese patients compared to control subjects. PAI-1 serum levels observed in obese patients were significantly lower (10.63 ± 4.82) compared to controls (14.26 ± 11.4; p < 0.05). No differences were observed in the PAI-1 4G/5G promoter genotypes frequencies (p = 0.12). No differences were observed in PAI-1 plasma levels among obese patients with liver fibrosis (10.64 ± 4.35) compared to patients without liver fibrosis (10.61 ± 5.2; p = 0.985). PAI-1 4G/5G promoter genotypes frequencies were similar in patients with or without liver fibrosis associated to NASH (p = 0.6).Conclusions. Morbidly obese patients had significantly lower PAI-1 serum levels with similar PAI-1 4G/5G genotypes frequencies compared to non-obese subjects. The frequency of 4G/5G genotypes in Chilean Hispanic healthy subjects was similar to that described in other populations. No association was found between PAI-1 serum levels or 4G/5G genotype with liver fi-brosis in obese patients.     

Demographic description and outcomes of a metropolitan network for myocardial infarction treatment

Objective:The objective of the study was to describe the myocardial infarction treatment network and compare in-hospital mortality in patients undergoing either primary angioplasty or pharmacoinvasive strategy in Mexico City and a broad metropolitan area.Methods:Cohort study including patients with ST-elevation myocardial infarction. We recorded demographic and clinical data, laboratory tests and in-hospital mortality in patients that underwent primary angioplasty and pharmacoinvasive strategy. Kaplan-Meier analysis was used to assess mortality and Cox-regression assessed mortality risk factors.Results:Three hundred forty patients from a network of 60 hospitals and 9 states were analyzed. Of the total population, 166 were treated with pharmacoinvasive strategy and 174 with primary angioplasty. Door to thrombolytic time was 54 min and door to wire crossing time was 72.5 min; no differences in total ischemia time were demonstrated. No differences for in-hospital mortality (6.3% vs. 5.4%, p = 0.49) were found when comparing pharmacoinvasive and primary angioplasty groups. The main predictors for in-hospital mortality were: glucose > 180 mg/dl (HR 3.73), total ischemia time > 420 min (HR 3.18), heart rate > 90 bpm (HR 5.46), Killip and Kimball > II (HR 11.03), and left ventricle ejection fraction < 40% (HR 3.21).Conclusions:This myocardial infarction network covers a large area and constitutes one of the biggest in the world. There were no differences regarding in-hospital mortality between pharmacoinvasive strategy and primary angioplasty. Pharmacoinvasive strategy is an effective and safe option for prompt reperfusion in Mexico.Key words: Myocardial infarction, Thrombolytic therapy, Angioplasty, Mortality     

The role of Fluorine-18-Fluorodeoxyglucose positron emission tomography in staging and restaging of patients with osteosarcoma

Background

The objective of this study is to systematically review the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) with Fluorine-18-Fluorodeoxyglucose (FDG) in patients with osteosarcoma (OS).

Methods

A comprehensive literature search of published studies through October 10^th, 2012 in PubMed/MEDLINE, Embase and Scopus databases regarding whole-body FDG-PET and FDG-PET/CT in patients with OS was performed.

Results

We identified 13 studies including 289 patients with OS. With regard to the staging and restaging of OS, the diagnostic performance of FDG-PET and PET/CT seem to be high; FDG-PET and PET/CT seem to be superior to bone scintigraphy and conventional imaging methods in detecting bone metastases; conversely, spiral CT seems to be superior to FDG-PET in detecting pulmonary metastases from OS

Conclusions

Metabolic imaging may provide additional information in the evaluation of OS patients. The combination of FDG-PET or FDG-PET/CT with conventional imaging methods seems to be a valuable tool in the staging and restaging of OS and may have a relevant impact on the treatment planning.