The Future in Sensing Technologies for Malaria Surveillance: A Review of Hemozoin-Based Diagnosis.

Early and effective malaria diagnosis is vital to control the disease spread and to prevent the emergence of severe cases and death. Currently, malaria diagnosis relies on optical microscopy and immuno-rapid tests; however, these require a drop of blood, are time-consuming, or are not specific and sensitive enough for reliable detection of low-level parasitaemia. Thus, there is an urge for simpler, prompt, and accurate alternative diagnostic methods. Particularly, hemozoin has been increasingly recognized as an attractive biomarker for malaria detection. As the disease proliferates, parasites digest host hemoglobin, in the process releasing toxic haem that is detoxified into an insoluble crystal, the hemozoin, which accumulates along with infection progression. Given its magnetic, optical, and acoustic unique features, hemozoin has been explored for new label-free diagnostic methods. Thereby, herein, we review the hemozoin-based malaria detection methods and critically discuss their challenges and potential for the development of an ideal diagnostic device.

Multilayer Thin-Film Optical Filters for Reflectance-Based Malaria Diagnostics.

Malaria diagnosis relies on optical microscopy and/or rapid diagnostic tests based on detecting specific malaria antigens. The clinical sensitivity of these methods is highly dependent on parasite density, with low levels of detection at low parasite density, challenging the worldwide malaria elimination efforts. Therefore, there is a need for diagnostic methods with higher sensitivity, demanding innovative diagnostics devices able to detect malaria at low parasite density and at early stages of the disease. We propose an innovative optical device for malaria diagnosis, based on optical reflectance spectrophotometry, for the detection of parasites through the quantification of haemozoin. For this purpose, a set of eight thin-film optical filters, based on multilayer stacks of MgO/TiO2 and SiO2/TiO2 thin-films, with high transmittance and low full width at half maximum (FWHM) at specific wavelengths, was designed and fully characterized (both numerically and experimentally). A preliminary assessment of its potential to reconstruct the original spectra of red blood cells was performed, both in uninfected and Plasmodium falciparum-infected samples. The obtained results show that, although the experimental filters have a non-ideal performance characteristic, they allow us to distinguish, based on only 8 discrete points in the optical spectrum, between healthy and malaria infected samples, up to a detection limit of 12 parasites/µL of red blood cells. Those results enhance the potential of using such a device for malaria diagnostics, aiming for non-invasiveness.

Synergistic Effect of Inflammatory Cytokines and Body Adiposity on Insulin Resistance and Endothelial Markers in Patients With Stages 3-5 Chronic Kidney Disease.

BACKGROUND: High body adiposity, inflammatory cytokines, insulin resistance (IR), and the endothelial markers-soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1)-are among cardiovascular risk factors observed in chronic kidney disease (CKD). Synergistic interaction of inflammatory cytokines with adiposity on IR, sICAM-1, and sVCAM-1 has not been reported in nondialysis-dependent CKD (NDD-CKD) patients. Thus the study aim was to evaluate the interaction of inflammatory cytokines on the association of body adiposity with the cardiometabolic risk factors-IR, sICAM-1, and sVCAM-1-in NDD-CKD patients. Cytokines association with estimated glomerular filtration rate (eGFR) and body adiposity was also examined. DESIGN AND METHODS: A cross-sectional study was conducted in an interdisciplinary outpatient Nephrology Clinic. SUBJECTS AND MEASUREMENTS: NDD-CKD adults with eGFR ≤60 mL/minute/1.73 m2 under regular treatment. Inflammatory cytokines, homeostasis model assessment of insulin resistance (HOMA-IR), sICAM-1, sVCAM-1, eGFR (by CKD-Epidemiology collaboration equation)-EPI equation, and body composition assessed by dual-energy X-ray absorptiometry and anthropometry were evaluated. Synergistic effects of inflammatory markers with body adiposity on studied cardiometabolic risk factors were assessed by interaction and mediation analysis. RESULTS: The study cohort comprised 241 NDD-CKD patients (54.8% men; eGFR = 29.4 ± 12.9 mL/minute/1.73 m2). Variables evaluated: Inflammatory cytokines were not associated with eGFR and not different among CKD stages. Percentage of total body adiposity (%TBA) was independently associated with tumor necrosis factor-alpha (TNFα) and HOMA-IR. Waist-to-height ratio was independently associated with TNFα, interleukin-8, monocyte chemoattractant protein-1 (MCP1), and HOMA-IR. Interaction analysis showed TNFα, interleukin-8, and MCP1 as independent mediators of the effects of high percentage of total body adiposity and waist-to-height ratio on HOMA-IR (P < .0001). Body adiposity did not associate with sICAM-1 and sVCAM-1. TNFα (ß = 0.40) and MCP1 (ß = 0.31) were independently associated with sVCAM-1 (P < .01). CONCLUSIONS: In NDD-CKD patients, inflammatory cytokines synergistically mediated the effects of body adiposity, enhancing the cardiometabolic risk. Inflammation was associated with sVCAM-1, but not with eGFR.

Modeling of the burst release from PLGA micro- and nanoparticles as function of physicochemical parameters and formulation characteristics.

A substantial drug release from poly(lactic-co-glycolic) acid (PLGA) micro- and nanoparticles can occur in the first hours of immersion, which is referred to as burst release. A strong burst release (when not intentional) is to be avoided as it decreases the efficacy of the treatment and could be dangerous to the host. In this work we analyze the total amount of drug released during burst and respective kinetics in relation to formulations characteristics, experimental conditions and drug molecular properties in 154 drug release experiments with 41 different drugs by partial least squares (PLS) and decision tree regression. The model created enables to quantify to which degree the physicochemical parameters control the burst release from PLGA particles. Our analysis shows that the amount of drug released during burst is mostly influenced by the formulation characteristics and the synthesis parameters, whereas the drug release kinetics is also influenced by the molecular properties of the drug. The variables that significantly influence the amount and kinetics of the burst release are discussed in detail and compared with findings from other researchers. The final regression models are shown to predict the release profile of a new drug, opening the possibility to be applied to systematically manipulate the burst release by means of designing an optimized drug delivery system.

Chemical characteristics of a heteropolysaccharide from Tylopilus ballouii mushroom and its antioxidant and anti-inflammatory activities.

Fucogalactomannan (FGM) is a non-sulphated polysaccharide isolated from the Tylopilus ballouii mushroom. We investigated the chemical characteristics of this FGM using HPLC, chemical methods, and NMR studies ((1)H, (13)C, (1)H/(13)C-HSQC and DEPT-135 spectroscopies) without chemical fragmentation. This polysaccharide consisted primarily of mannose and galactose with variable amounts of fucose and traces of xylose and with MW of 140kDa. Infrared and NMR spectroscopies showed the possible interaction between these polysaccharides and proteins. The antioxidant activity showed for FGM a high inhibition of superoxide and hydroxyl radicals with an IC50 of 1.25 and 1.6mg/mL, respectively. The results of peroxidation tests showed that FGM had an IC50 of 1.72mg/mL. Furthermore, the anti-inflammatory assay showed that FGM reduced edema by 32.8%, 42.0%, and 56% at doses of 30, 50, and 70mg/kg, respectively. Thus, these results suggested a structure and indicated possible anti-inflammatory and antioxidant activities use of these polysaccharides.

Biological activities of the sulfated polysaccharide from the vascular plant Halodule wrightii

A sulfated polysaccharide (SPSG) was successfully isolated from seagrass Halodule wrightii Asch., Cymodoceaceae, and its antioxidant and anticoagulant activities were investigated. The data presented here showed that the SPSG is a 11 kDa sulfated heterogalactan with a sulfatation degree of 20.63 percent and it also contains glucose and xylose. SPSG antioxidant activities were evaluated using several in vitro assays and the anticoagulant activity was evaluated by aPTT and PT tests. These assays suggested that the SPSG possessed remarkable antioxidant properties in different in vitro assays and an outstanding anticoagulant activity 2.5-fold higher than that of heparin Clexane® in the aPTT test. This data represents the first reported on the sulfated polysaccharide biological activities from seagrass. These results indicate that SPSG can be considered in the future as a drug utilized in treating diseases from these systems.

Medial contact and smaller plantar loads characterize individuals with Patellofemoral Pain Syndrome during stair descent.

OBJECTIVES: To investigate plantar pressure distribution in individuals with and without Patellofemoral Pain Syndrome during the support phase of stair descent. DESIGN: Observational case-control study. PARTICIPANTS: 30 young adults with Patellofemoral Pain Syndrome and 44 matched controls. MAIN OUTCOME MEASURES: Contact area, peak pressure and pressure-time integral (Novel Pedar-X system) were evaluated in six plantar areas (medial, central and lateral rearfoot; midfoot; medial and lateral forefoot) during stair descent. RESULTS: Contact area was greater in the Patellofemoral Pain Syndrome Group at medial rearfoot (p = 0.019) and midfoot (p < 0.001). Subjects with Patellofemoral Pain Syndrome presented smaller peak pressures (p < 0.001). CONCLUSION: The pattern of plantar pressure distribution during stair descent in Patellofemoral Pain Syndrome subjects was different from controls. This seems to be related to greater medial rearfoot and midfoot support. Smaller plantar loads found in Patellofemoral Pain Syndrome subjects during stair descent reveal a more cautious motor pattern in a challenging task.

A non-anticoagulant heterofucan has antithrombotic activity in vivo.

Fucan is a term used to denominate a family of sulfated L-fucose-rich polysaccharides. The brown alga Spatoglossum schröederi (Dictyotaceae) has three heterofucans namely fucan A, B and C. The 21 kDa fucan A is composed of a core of a beta (1-3) glucuronic acid-containing oligosaccharide of 4.5 kDa with branches at C4 of the fucose chains alpha (1-3) linked. The fucose is mostly substituted at C4 with a sulfate group and at C2 with chains of beta (1-4) xylose. This fucan has neither anticoagulant (from from 0.1 to 100 microg) nor hemorrhagic activities (from 50 to 800 microg/mL). The antithrombotic test in vivo showed that fucan A has no activity in any of the concentrations (from 0.2 to 20 microg/g/day) tested 1 h after polysaccharide administration. However, when fucan A was injected endovenously 24 h before the ligature of the venae cavae, we observed a dose-dependent effect, reaching saturation at around 20 microg/g of rat weight. In addition, this effect is also time-dependent, reaching saturation around 16 h after fucan administration. In addition, regardless of the administration route, fucan A displayed antithrombotic activity. The exception was the oral pathway. Of particular importance was the finding that fucan A stimulates the synthesis of an antithrombotic heparan sulfate from endothelial cells like heparin. The hypothesis has been raised that the in vivo antithrombotic activity of fucan A is related to the increased production of this heparan. Taken together with the fact that the compound is practically devoid of anticoagulant and hemorrhagic activity, the data suggest that it may be an ideal antithrombotic agent in vivo.