Inhibition of dendritic cell maturation by malaria is dose dependent and does not require Plasmodium falciparum erythrocyte membrane protein 1

Red blood cells infected with Plasmodium falciparum (iRBCs) have been shown to modulate maturation of human monocyte-derived dendritic cells (DCs), interfering with their ability to activate T cells. Interaction between Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) and CD36 expressed by DCs is the proposed mechanism, but we show here that DC modulation does not require CD36 binding, PfEMP1, or contact between DCs and infected RBCs and depends on the iRBC dose. iRBCs expressing a PfEMP1 variant that binds chondroitin sulfate A (CSA) but not CD36 were phagocytosed, inhibited lipopolysaccharide (LPS)-induced phenotypic maturation and cytokine secretion, and abrogated the ability of DCs to stimulate allogeneic T-cell proliferation. CD36- and CSA-binding iRBCs showed comparable inhibition. P. falciparum lines rendered deficient in PfEMP1 expression by targeted gene knockout or knockdown also inhibited LPS-induced phenotypic maturation, and separation of DCs and iRBCs in transwells showed that inhibition was not contact dependent. Inhibition was observed at an iRBC:DC ratio of 100:1 but not at a ratio of 10:1. High doses of iRBCs were associated with apoptosis of DCs, which was not activation induced. Lower doses of iRBCs stimulated DC maturation sufficient to activate autologous T-cell proliferation. In conclusion, modulation of DC maturation by P. falciparum is dose dependent and does not require interaction between PfEMP1 and CD36. Inhibition and apoptosis of DCs by high-dose iRBCs may or may not be physiological. However, our observation that low-dose iRBCs initiate functional DC maturation warrants reevaluation and further investigation of DC interactions with blood-stage P. falciparum.     

Biodistribution and Pharmacokinetics of Dapivirine-Loaded Nanoparticles after Vaginal Delivery in Mice

Purpose

To assess the potential of polymeric nanoparticles (NPs) to affect the genital distribution and local and systemic pharmacokinetics (PK) of the anti-HIV microbicide drug candidate dapivirine after vaginal delivery.

Methods

Dapivirine-loaded, poly(ethylene oxide)-coated poly(epsilon-caprolactone) (PEO-PCL) NPs were prepared by a nanoprecipitation method. Genital distribution of NPs and their ability to modify the PK of dapivirine up to 24 h was assessed after vaginal instillation in a female mouse model. Also, the safety of NPs upon daily administration for 14 days was assessed by histological analysis and chemokine/cytokine content in vaginal lavages.

Results

PEO-PCL NPs (180–200 nm) were rapidly eliminated after administration but able to distribute throughout the vagina and lower uterus, and capable of tackling mucus and penetrate the epithelial lining. Nanocarriers modified the PK of dapivirine, with higher drug levels being recovered from vaginal lavages and vaginal/lower uterine tissues as compared to a drug suspension. Systemic drug exposure was reduced when NPs were used. Also, NPs were shown safe upon administration for 14 days.

Conclusions

Dapivirine-loaded PEO-PCL NPs were able to provide likely favorable genital drug levels, thus attesting the potential value of using this vaginal drug delivery nanosystem in the context of HIV prophylaxis.     

Recycled Mortars with Ceramic Aggregates. Pore Network Transmutation and Its Relationship with Physical and Mechanical Properties

The porosity of mortars with recycled ceramic aggregates (10, 20, 30, 50, and 100% as a replacement of natural aggregate) was evaluated and analyzed using three different techniques. The results of gas adsorption (N₂), Scanning Electron Microscopy (SEM) image analysis and open porosity allowed establishing the relationship between the recycled aggregate content and the porosity of these mortars, as well as the relationship between porosity and the physical and mechanical properties of the mortars: absorption, density, compressive strength, modulus of elasticity, and drying shrinkage. Using the R² coefficient and the equation typology as criteria, additional data such as Brunauer, Emmett, and Teller (BET) surface area (N₂ adsorption) established significant correlations with the mentioned properties; with SEM image analysis, no explanatory relationships could be established; and with open porosity, revealing relationships were established (R² > 0.9). With the three techniques, it was confirmed that the increase in porosity is related to the increase in the amount of ceramic aggregate; in particular with gas adsorption (N₂) and open porosity. It was concluded that the open porosity technique can explain the behavior of these recycled mortars with more reliable data, in a simple and direct way, linked to its establishment with a more representative sample of the mortar matrix.     

Epidemiological and clinical characteristics of community‐acquired and nosocomial influenza cases and risk factors associated with complications: A four season analysis of all adult patients admitted in a tertiary hospital

BackgroundInformation on the characteristics of patients with nosocomial influenza and associated complications is scarce. This study compared epidemiological and clinical characteristics of patients admitted with hospital‐acquired influenza (HAI) to those with community‐acquired influenza (CAI) and analyzed risk factors associated with complications.MethodsThis retrospective, observational study included all adult patients with confirmed influenza virus infection admitted to Son Espases University Hospital during the influenza season in Spain (October to May) from 2012‐2013 to 2015‐2016. Symptom onset before admission was included as CAI, and 2 days after admission or within 48 hours after previous discharge were considered as HAI.ResultsOverall, 666 patients with laboratory‐confirmed influenza were included; 590 (88.6%) and 76 (11.4%) had CAI and HAI, respectively. Baseline characteristics and vaccination rates were similar in both groups. Patients with HAI had significantly fewer symptoms, less radiological alterations, and earlier microbiological diagnosis than those with CAI. Eighty‐five (14.4%) and 20 (27.6%) CAI and HAI patients, respectively, experienced at least one complication, including septic shock, admission to the intensive care unit, mechanical ventilation or evolution to death (any one, P = .003). Univariate and multivariate binary logistic regression was performed to assess independent risk factors associated with the occurrence of complications: nosocomial infection, diabetes, oseltamivir treatment, having received no vaccination, microbiological delay, dyspnea, and the state of confusion were the most important significant factors.ConclusionsOur study shows the need to implement microbiological diagnostic measures in the first 48 hours to reduce HAI frequency and associated complications.     

Sexual behaviour and infection rates for HIV, blood-borne and sexually transmitted infections among patients attending drug treatment centres in Rio de Janeiro, Brazil

A survey was carried out in 2 drug use treatment centres (TCs) in Rio de Janeiro, Brazil, to assess risk behaviours, HIV infection and other sexually transmitted infections/blood-borne infections (STIs/BBIs). Two hundred and twenty-five drug users (195 males and 30 females) were interviewed and clinically examined, and their blood and urine were tested for STIs/BBIs. Prevalences (%) for these infections were as follows--HIV: 0.9, hepatitis B virus (HBV): 14.7, hepatitis C virus (HCV): 5.8, syphilis: 5.3, gonorrhoea/chlamydia (CT/NG): 4.7. In bivariate analyses CT/NG infection was associated with younger age (P=0.003); current genitourinary symptoms (odds ratio [OR]=6.2) and a mainly illegal source of income (OR=9.1). Hepatitis C infection was associated with a history of ever having injected any drug (OR=19.6), and with each one of the injected drugs. After multiple logistic regression, lower educational level (adjusted odds ratio [AOR]=3.70) and 'ever having injected drugs' (AOR=3.69) remained as independent risk factors for hepatitis B infection. In conclusion, TCs must implement programmes directed towards the prevention of STIs/BBIs.     

Effect of dietary hydrogenated fish oil on the plasma lipoprotein profile and on the fatty acid composition of different tissues on the rat

Dietary fatty acids are actively incorporated into membrane lipids, and fat intake can modify the composition and the biochemical activity of cellular membranes and the pattern of plasma lipoproteins. Industrial hydrogenation of polyunsaturated oils leads to the formation of isomeric trans fatty acids which are incorporated into cellular membranes when they are present in the diet. The trans fatty acid amount present in hydrogenated oils depends on the degree of hydrogenation, being high for partially hydrogenated oils and low for highly hydrogenated oils. Hydrogenated fish oil is widely used in some countries for the production of margarine and industrial fats. This study compares the fatty acid composition of plasma, erythrocytes, subcutaneous adipose tissue, and hepatic microsomal membranes and the plasma lipoprotein profile after feeding rats with a synthetic diet containing either fish oil, partially hydrogenated fish oil, or highly hydrogenated fish oil. It is observed that the tissue content of monounsaturated fatty acids increases and that the content of polyunsaturated fatty acids decreases after an increase of the degree of hydrogenation of the dietary fat. Tissues from animals fed partially hydrogenated fish oil show significant amounts of trans fatty acids only. The plasma triacylglyceride composition and the lipoprotein profile are also altered by the degree of hydrogenation of the dietary fat. Triacylglycerides decrease after highly hydrogenated fat feeding only. Total cholesterol and low-density lipoprotein cholesterol are significantly increased after partially hydrogenated fat feeding. Although no direct evidence is presented, this effect may be attributable to the high content of trans isomers of this dietary fat which nutritionally may behave as saturated fatty acids.     

Immunostimulatory activity of low-molecular-weight hyaluronan on dendritic cells stimulated with Aggregatibacter actinomycetemcomitans or Porphyromonas gingivalis

Clinical Oral Investigations - Periodontitis is a chronic inflammatory disease characterized by tooth-supporting tissue destruction, which is elicited by the host’s immune response triggered...     

A before-school physical activity intervention to improve cognitive parameters in children: The Active-Start study

The aim of the study was threefold: (a) to test a before-school physical activity intervention (Active-Start) on academic performance, selective attention, and concentration capacity; (b) to test the effect of the Active-Start intervention on anthropometry, body composition, and physical fitness parameters; and (c) whether the physical fitness components are moderators of the effect of the Active-Start program on academic performance, selective attention, and concentration capacity in Chilean children. The Active-Start intervention was a RCT which comprised 170 children (8-10 years old) from three public schools with low socioeconomic status from the city of Santiago (Chile). The exercise intervention was delivered daily, before starting the first school-class (8:00-8:30 am ) for 8 weeks. Changes in academic performance, selective attention and concentration capacity, anthropometric, body composition, and physical fitness parameters were measured. The analyses used were mixed regression models for repeated measures over time. No statistically significant changes in attention and concentration capacity were found. However, significant changes were seen in language (0.63; 95% CI 0.49-0.77) and mathematics (0.49; 95% CI 0.32-0.66) performance (P < .001). Also, improvements were seen in fat mass, fat-free mass, muscular, and cardiorespiratory fitness (all P < .05). The Johnson-Neyman technique revealed a significant relationship between the effect of intervention and attention and concentration when change in cardiorespiratory fitness was above, but not below, 3.05 and 0.70 mL/kg/min, respectively. Implementing before-school physical activity programs such as the Active-Start to enhance the cardiorespiratory fitness may benefit attention capacity and academic success among schoolchildren.