Aptamers for the Delivery of Plant-Based Compounds: A Review.

Natural compounds have a high potential for the treatment of various conditions, including infections, inflammatory diseases, and cancer. However, they usually present poor pharmacokinetics, low specificity, and even toxicity, which limits their use. Therefore, targeted drug delivery systems, typically composed of a carrier and a targeting ligand, can enhance natural product selectivity and effectiveness. Notably, aptamers-short RNA or single-stranded DNA molecules-have gained attention as promising ligands in targeted drug delivery since they are simple to synthesize and modify, and they present high tissue permeability, stability, and a wide array of available targets. The combination of natural products, namely plant-based compounds, with a drug delivery system utilizing aptamers as targeting agents represents an emerging strategy that has the potential to broaden its applications. This review discusses the potential of aptamers as targeting agents in the delivery of natural compounds, as well as new trends and developments in their utilization in the field of medicine.

Targeting proto-oncogene B-MYB G-quadruplex with a nucleic acid-based fluorescent probe.

The B-MYB gene encodes a transcription factor (B-MYB) that regulates cell growth and survival. Abnormal expression of B-MYB is frequently observed in lung cancer and poses challenges for targeted drug therapy. Oncogenes often contain DNA structures called G-quadruplexes (G4s) in their promoter regions, and B-MYB is no exception. These G4s play roles in genetic regulation and are potential cancer treatment targets. In this study, a probe was designed to specifically identify a G4 within the promoter region of the B-MYB gene. This probe combines an acridine derivative ligand with a DNA segment complementary to the target sequence, enabling it to hybridize with the adjacent sequence of the G4 being investigated. Biophysical studies demonstrated that the acridine derivative ligands C5NH2 and C8NH2 not only effectively stabilized the G4 structure but also exhibited moderate affinity. They were capable of altering the G4 topology and exhibited enhanced fluorescence emission in the presence of this quadruplex. Additionally, these ligands increased the number of G4s observed in cellular studies. Through various biophysical studies, the target sequence was shown to form a G4 structure, even with an extra nucleotide tail added to its flanking region. Cellular studies confirmed the co-localization between the target sequence and the developed probe.

Targeting of G-quadruplex DNA with 99mTc(I)/Re(I) Tricarbonyl Complexes Carrying Pyridostatin Derivatives.

The main goal of this work was to elucidate the potential relevance of (radio)metal chelates of 99mTc and Re targeting G-quadruplex structures for the design of new tools for cancer theranostics. 99mTc provides the complexes with the ability to perform single-photon-emission computed tomography imaging studies, while the Re complexes should act as anticancer agents upon interaction with specific G4 DNA or RNA structures present in tumor tissues. Towards this goal, we have developed isostructural 99mTc(I) and Re(I) tricarbonyl complexes anchored by a pyrazolyl-diamine (Pz) chelator carrying a pendant pyridostatin (PDS) fragment as the G4-binding motif. The interaction of the PDF-Pz-Re (8) complex with different G4-forming oligonucleotides was studied by circular dichroism, fluorescence spectroscopy and FRET-melting assays. The results showed that the Re complex retained the ability to bind and stabilize G4-structures from different DNA or RNA sequences, namely those present on the SRC proto-oncogene and telomeric RNA (TERRA sequence). PDF-Pz-Re (8) showed low to moderate cytotoxicity in PC3 and MCF-7 cancer cell lines, as typically observed for G4-binders. Biodistribution studies of the congener PDF-Pz-99mTc (12) in normal mice showed that the complex undergoes a fast blood clearance with a predominant hepatobiliary excretion, pointing also for a high in vitro stability.

Quantitative Analysis of Viscoelastic Properties of Red Blood Cells using Optical Tweezers and Defocusing Microscopy.

The viscoelastic properties of erythrocytes have been investigated by a range of techniques. However, the reported experimental data vary. This is not only attributed to the normal variability of cells, but also to the differences in methods and models of cell response. Here, an integrated protocol using optical tweezers and defocusing microscopy is employed to obtain the rheological features of red blood cells in the frequency range of 1 Hz to 35 Hz. While optical tweezers are utilized to measure the erythrocyte-complex elastic constant, defocusing microscopy is able to obtain the cell height profile, volume, and its form factor a parameter that allows conversion of complex elastic constant into complex shear modulus. Moreover, applying a soft glassy rheology model, the scaling exponent for both moduli can be obtained. The developed methodology allows to explore the mechanical behavior of red blood cells, characterizing their viscoelastic parameters, obtained under well-defined experimental conditions, for several physiological and pathological conditions.

Wafer-sized WS2 monolayer deposition by sputtering.

We demonstrate that tungsten disulphide (WS2) with thicknesses ranging from monolayer (ML) to several monolayers can be grown on SiO2/Si, Si, and Al2O3 by pulsed direct current-sputtering. The presence of high quality monolayer and multilayered WS2 on the substrates is confirmed by Raman spectroscopy since the peak separations between the A1g-E2g and A1g-2LA vibration modes exhibit a gradual increase depending on the number of layers. X-ray diffraction confirms a textured (001) growth of WS2 films. The surface roughness measured with atomic force microscopy is between 1.5 and 3 Å for the ML films. The chemical composition WSx (x = 2.03 ± 0.05) was determined from X-ray Photoelectron Spectroscopy. Transmission electron microscopy was performed on a multilayer film to show the 2D layered structure. A unique method for growing 2D layers directly by sputtering opens up the way for designing 2D materials and batch production of high-uniformity and high-quality (stochiometric, large grain sizes, flatness) WS2 films, which will advance their practical applications in various fields.

Prognostic Value of the Malnutrition-inflammation Score in Hospitalization and Mortality on Long-term Hemodialysis.

OBJECTIVE: Since its development, cumulative evidence has accumulated regarding the prognostic value of the Malnutrition-Inflammation Score (MIS/Kalantar score) prognostic value; however, there is a shortage of recent and large studies with comprehensive statistical methodologies that contribute to support a higher level of evidence and a consensual cutoff. The aim of this study was to assess the strength of MIS association with hospitalization and mortality in a nationwide cohort. METHODS: This was a historical cohort study of hemodialysis patients from 25 outpatient centers followed up for 48 months. Univariable and multivariable Cox additive regression models were used to analyze the data. The C-index was estimated to assess the performance of the final model. RESULTS: Two thousand four hundred forty-four patients were analyzed, 59.0% males, 32.0% diabetic, and median age of 71 years (P25 = 60, P75 = 79). During a median period of 45-month follow-up, with a maximum of 48 months (P25 = 31; P75 = 48), 875 patients presented an MIS <5 (35.8%) and 860 patients (35.2%) died. The proportion of deaths was 23.1% for patients with the MIS <5 and 41.9% if the MIS ≥5 (P < .001). A total of 1,528 patients (62.5%) were hospitalized with a median time to the first hospitalization of 26 months (P25 = 9; P75 = 45). A new cutoff point regarding the risk of death, MIS ≥6, was identified for this study data set. In multivariable analysis for hospitalization risk, a higher MIS, higher comorbidity index, and arteriovenous graft or catheter increased the risk, whereas higher Kt/V and higher albumin had a protective effect. In multivariable analysis for mortality risk, adjusting for age, albumin, normalized protein catabolic rate, Charlson comorbidity index, interdialytic weight gain, Kt/V, diabetes, hematocrit, and vascular access, patients with the MIS ≥6 showed a hazard ratio of 1.469 (95% confidence interval: 1.262-1.711; P < .001). Higher age, higher interdialytic weight gain, higher comorbidity index, and catheter increased significantly the risk, whereas higher Kt/V, higher albumin, and higher normalized protein catabolic rate (≥1.05 g/kg/d) reduced the risk. CONCLUSION: The MIS maintains its relevant and significant association with hospitalization and mortality.

Data sharing and collaborations with Telco data during the COVID-19 pandemic: A Vodafone case study.

With the outbreak of COVID-19 across Europe, anonymized telecommunications data provides a key insight into population level mobility and assessing the impact and effectiveness of containment measures. Vodafone's response across its global footprint was fast and delivered key new metrics for the pandemic that have proven to be useful for a number of external entities. Cooperation with national governments and supra-national entities to help fight the COVID-19 pandemic was a key part of Vodafone's response, and in this article the different methodologies developed are analyzed, as well as the key collaborations established in this context. In this article we also analyze the regulatory challenges found, and how these can pose a risk of the full benefits of these insights not being harnessed, despite clear and efficient Privacy and Ethics assessments to ensure individual safety and data privacy.

Multi-infusion with integrated multiple pressure sensing allows earlier detection of line occlusions.

BACKGROUND: Occlusions of intravenous (IV) tubing can prevent vital and time-critical medication or solutions from being delivered into the bloodstream of patients receiving IV therapy. At low flow rates (≤ 1 ml/h) the alarm delay (time to an alert to the user) can be up to 2 h using conventional pressure threshold algorithms. In order to reduce alarm delays we developed and evaluated the performance of two new real-time occlusion detection algorithms and one co-occlusion detector that determines the correlation in trends in pressure changes for multiple pumps. METHODS: Bench-tested experimental runs were recorded in triplicate at rates of 1, 2, 4, 8, 16, and 32 ml/h. Each run consisted of 10 min of non-occluded infusion followed by a period of occluded infusion of 10 min or until a conventional occlusion alarm at 400 mmHg occurred. The first algorithm based on binary logistic regression attempts to detect occlusions based on the pump's administration rate Q(t) and pressure sensor readings P(t). The second algorithm continuously monitored whether the actual variation in the pressure exceeded a threshold of 2 standard deviations (SD) above the baseline pressure. When a pump detected an occlusion using the SD algorithm, a third algorithm correlated the pressures of multiple pumps to detect the presence of a shared occlusion. The algorithms were evaluated using 6 bench-tested baseline single-pump occlusion scenarios, 9 single-pump validation scenarios and 7 multi-pump co-occlusion scenarios (i.e. with flow rates of 1 + 1, 1 + 2, 1 + 4, 1 + 8, 1 + 16, and 1 + 32 ml/h respectively). Alarm delay was the primary performance measure. RESULTS: In the baseline single-pump occlusion scenarios, the overall mean ± SD alarm delay of the regression and SD algorithms were 1.8 ± 0.8 min and 0.4 ± 0.2 min, respectively. Compared to the delay of the conventional alarm this corresponds to a mean time reduction of 76% (P = 0.003) and 95% (P = 0.001), respectively. In the validation scenarios the overall mean ± SD alarm delay of the regression and SD algorithms were respectively 1.8 ± 1.6 min and 0.3 ± 0.2 min, corresponding to a mean time reduction of 77% and 95%. In the multi-pump scenarios a correlation > 0.8 between multiple pump pressures after initial occlusion detection by the SD algorithm had a mean ± SD alarm delay of 0.4 ± 0.2 min. In 2 out of the 9 validation scenarios an occlusion was not detected by the regression algorithm before a conventional occlusion alarm occurred. Otherwise no occlusions were missed. CONCLUSIONS: In single pumps, both the regression and SD algorithm considerably reduced alarm delay compared to conventional pressure limit-based detection. The SD algorithm appeared to be more robust than the regression algorithm. For multiple pumps the correlation algorithm reliably detected co-occlusions. The latter may be used to localize the segment of tubing in which the occlusion occurs. Trial registration Not applicable.

Protocol to measure the membrane tension and bending modulus of cells using optical tweezers and scanning electron microscopy.

The elastic properties of cell membranes, particularly the membrane tension and bending modulus, are known to be key regulators of cellular functions. Here, we present a correlative and integrated tool based on optical tweezers and scanning electron microscopy to accurately determine these properties in a variety of cell types. Although there are intrinsic difficulties associated with correlative experiments, we believe that the methods presented can be considered a suitable protocol for determining the elastic properties of cell membranes. For complete details on the use and execution of this protocol, please refer to Soares et al. (2020).

Spontaneous self-assembly and structure of perfluoroalkylalkane surfactant hemimicelles by molecular dynamics simulations.

Fully atomistic molecular-dynamics (MD) simulations of perfluoroalkylalkane molecules at the surface of water show the spontaneous formation of aggregates whose size and topography closely resemble the experimentally observed hemimicelles for this system. Furthermore, the grazing incidence X-ray diffraction (GIXD) pattern calculated from the simulation trajectories reproduces the experimental GIXD spectra previously obtained, fully validating the MD simulation results. The detailed analysis of the internal structure of the aggregates obtained by the MD simulations supports a definite rational explanation for the spontaneous formation, stability, size, and shape of perfluoroalkylalkane hemimicelles at the surface of water.

Percutaneous Ablation Versus Nephrectomy for Small Renal Masses: Clinical Outcomes in a Single-Center Cohort.

PURPOSE: To compare the outcomes of percutaneous ablation (PA) versus nephrectomy (NE) for small renal masses (SRMs) in patients with T1 renal cell carcinoma and evaluate the role of pre-procedural biopsy in the treatment of SRM. MATERIALS AND METHODS: Retrospective cohort analysis of patients subjected to PA or NE for SRM (< 5 cm) from January 2006 to August 2016. A total of 231 patients with T1 SRM were included in the main analysis. Patient demographics, tumor characteristics, biopsy and procedural details, clinical outcomes, complication rates, and changes in renal function were compared in patients with malignant SRMs. Survival rates were compared using log-rank test. RESULTS: A total of 142 patients underwent PA and 89 patients underwent NE, with a respective mean follow-up period of 2.50 (SD 1.77) and 1.85 (SD 0.97) years (P = 0.029). Rate of intervention for benign tumors was similar in PA (n = 21, 15%) and NE (n = 16, 18%; P = 0.520) without routine pre-procedural biopsy. Routine pre-procedural biopsy resulted in zero benign tumors treated in the PA cohort. Tumor recurrence was similar and cumulative survival was similar in both groups (P = 0.287). Residual tumor was observed in 18 PA patients. Complication rates were lower for PA than for NE (9 vs 30%, P < 0.001). A significant reduction in eGFR was observed after NE (12.1 mL/min/1.73 m2; P = 0.009) relative to PA (5.9 mL/min/1.73 m2; P = 0.060). CONCLUSION: PA is a safe alternative to NE in the treatment of SRM, with similar overall survival and decreased complication rates. Pre-procedural biopsy decreases the rate of intervention for benign tumors and should be routinely performed.

Dual-Energy CT Iodine Mapping and 40-keV Monoenergetic Applications in the Diagnosis of Acute Bowel Ischemia.

OBJECTIVE: Sensitivity of CT of the abdomen for detection of acute bowel ischemia (ABI) can be as low as 60%. In this study, we assessed the diagnostic performance of iodine-map and monoenergetic (40-keV) images in patients with suspected ABI. MATERIALS AND METHODS: This retrospective study included 60 consecutive patients with suspected ABI who underwent a standardized imaging protocol dual-source dual-energy CT (DECT) over a 26-month period. Clinical and operative outcomes were recorded as the reference standard. Two abdominal radiologists who were unaware of clinical and surgical information independently assessed conventional CT images for ABI. After a time interval designed to reduce recall, readers reassessed conventional images with supplementary iodine-map and 40-keV postprocessed images. Quantitative ROI analysis was also performed. RESULTS: ABI was observed in 11 patients. For reader A, sensitivity was 63.6% (95% CI, 30.8-89.1%) when interpreting conventional images alone. Sensitivity for detection of ABI increased to 81.8% (95% CI, 48.2-97.7%) and 100% (95% CI, 71.5-100%) when iodine-map and 40-keV images were assessed, respectively. For reader B, no change in sensitivity was seen with either technique, but the number of false-positives were reduced with supplementary iodine-map and 40-keV postprocessed images. Interobserver agreement was fair with conventional images (κ = 0.29) but improved to moderate (κ = 0.45) and substantial (κ = 0.63) with iodine-map and 40-keV images, respectively. Quantitative assessment found significant differences in iodine uptake (1.01 ± 0.55 mg/mL vs 3.04 ± 1.19 mg/mL) and mean attenuation (75.2 ± 38.4 HU vs 163.5 ± 48.9 HU) between nonischemic and ischemic segments, respectively. CONCLUSION: Iodine-map and 40-keV monoenergetic images increase conspicuity of ABI, resulting in improved diagnostic accuracy compared with review of conventional CT images alone.

Major, minor, trace and rare earth elements in sediments of the Bijagós archipelago, Guinea-Bissau.

Sixty sediment samples from four sites in the Bijagós archipelago were characterized for fine fraction, loss on ignition, major, minor and trace elemental composition (Al, Fe, Ca, Mg, Ti, P, Zr, Mn, Cr, Sr, Ba, B, V, Li, Zn, Ni, Pb, As, Co, U, Cu, Cs and Cd), and the elements of the La-Lu series. Element concentrations were largely explained by the Al content and the proportion of fine fraction content, with the exception of Ca and Sr. Sediments showed enhanced Ti, U, Cr, As and Cd concentrations with respect to estimated upper crust values, most likely mirroring a regional signature. Rare earth elements were in deficit relatively to the North American Shale Composite (NASC), mainly in coarser material. No pronounced Ce-anomaly was observed, while Eu-anomalies were positive in most analyzed sediments.

Evidence for contrasting accumulation pattern of cadmium in relation to other elements in Senilia senilis and Tagelus adansoni from the Bijagós archipelago, Guinea-Bissau.

Shellfish harvesting in intertidal areas is a widespread and economically important activity in many countries across West Africa. However, in some areas, there is virtually no information concerning the levels of contaminants (and other elements related to nutritional aspects) in the harvested species. We collected sediments and several individuals of the West African bloody cockle Senilia senilis and of the razor clam Tagelus adansoni during the dry season of 2015 nearby three islands in the Bijagós archipelago, Guinea-Bissau. Aluminium, Ca, Fe, Mg, As, Cd, Co, Cr, Cu, Mn, Ni, Pb and Zn were determined in sediments and whole soft tissues of the two bivalves. Sediments showed uniformly low trace element concentrations, pointing to an ecosystem with low levels of trace element contamination. T. adansoni presented higher concentrations of most elements than S. senilis, with the exception of Cd that showed up to 40 times higher values in S. senilis than in T. adansoni from the same sites. Furthermore, Cd concentrations (25±8.7 mg kg-1, dw) in S. senilis are clearly above the maximum level established for human consumption. Future studies should clarify whether biological factors are the major responsible for this unusual situation.

Plastic and other microfibers in sediments, macroinvertebrates and shorebirds from three intertidal wetlands of southern Europe and west Africa.

Microplastics are widespread in aquatic environments and can be ingested by a wide range of organisms. They can also be transferred along food webs. Estuaries and other tidal wetlands may be particularly prone to this type of pollution due to their particular hydrological characteristics and sewage input, but few studies have compared wetlands with different anthropogenic pressure. Furthermore, there is no information on microplastic transfer to secondary intertidal consumers such as shorebirds. We analysed intertidal sediments, macroinvertebrates and shorebirds, from three important wetlands along the Eastern Atlantic (Tejo estuary, Portugal; Banc d'Arguin, Mauritania and Bijagós archipelago, Guinea-Bissau), in order to evaluate the prevalence and transfer of microplastics along the intertidal food web. We further investigated variables that could explain the distribution of microplastics within the intertidal areas of the Tejo estuary. Microfibers were recorded in a large proportion of sediment samples (91%), macroinvertebrates (60%) and shorebird faeces (49%). µ-FTIR analysis indicated only 52% of these microfibers were composed of synthetic polymers (i.e. plastics). Microfiber concentrations were generally higher in the Tejo and lower in the Bijagós, with intermediate values for Banc d'Arguin, thus following a latitudinal gradient. Heavier anthropogenic pressure in the Tejo explains this pattern, but the relatively high concentrations in a pristine site like the Banc d'Arguin demonstrate the spread of pollution in the oceans. Similar microfiber concentrations in faeces of shorebirds with different foraging behaviour and similar composition of fibres collected from invertebrate and faeces suggest shorebirds mainly ingest microfibers through their prey, confirming microfiber transfer along intertidal food webs. Within the Tejo estuary, concentration of microfibers in the sediment and bivalves were positively related with the percentage of fine sediments and with the population size of the closest township, suggesting that hydrodynamics and local domestic sewage are the main factors influencing the distribution of microfibers.

Influence of age and sex on winter site fidelity of sanderlings Calidris alba.

Many migratory bird species show high levels of site fidelity to their wintering sites, which confers advantages due to prior knowledge, but may also limit the ability of the individual to move away from degrading sites or to detect alternative foraging opportunities. Winter site fidelity often varies among age groups, but sexual differences have seldom been recorded in birds. We studied a population of individually colour-marked sanderlings wintering in and around the Tejo estuary, a large estuarine wetland on the western coast of Portugal. For 160 individuals, sighted a total of 1,249 times between November 2009 and March 2013, we calculated the probability that they moved among five distinct wintering sites and how this probability is affected by distance between them. To compare site fidelity among age classes and sexes, as well as within the same winter and over multiple winters, we used a Site Fidelity Index (SFI). Birds were sexed using a discriminant function based on biometrics of a large set of molecularly sexed sanderlings (n = 990). The vast majority of birds were observed at one site only, and the probability of the few detected movements between sites was negatively correlated with the distance among each pair of sites. Hardly any movements were recorded over more than 15 km, suggesting small home ranges. SFI values indicated that juveniles were less site-faithful than adults which may reflect the accumulated knowledge and/or dominance of older animals. Among adults, females were significantly less site faithful than males. A sexual difference in winter site fidelity is unusual in shorebirds. SFI values show site-faithfulness is lower when multiple winters were considered, and most birds seem to chose a wintering site early in the season and use that site throughout the winter. Sanderlings show a very limited tendency to explore alternative wintering options, which might have implications for their survival when facing habitat change or loss (e.g., like severe beach erosion as can be the case at one of the study sites).

The current utility of ultrasound in the diagnosis of acute appendicitis.

The purpose of this study is to evaluate the current performance of ultrasound in the diagnosis of acute appendicitis. Retrospectively, patients who presented to a single institution between 2011 and 2012 were included. Diagnostic accuracy was calculated, with surgery considered gold-standard. Our data demonstrates that US relative to surgery-confirmed appendicitis has a sensitivity and specificity of 48.4% and 97.9%, respectively. The diagnostic accuracy was further increased when there was a low pre-test probability, with a NPV of up to 96.6%. Ultrasound has a strong PPV in the diagnosis of acute appendicitis, and in equivocal cases, the NPV is reliable.

Dual-Energy Computed Tomography: Advantages in the Acute Setting.

The aim of this article is to inform and update emergency radiologists in respect of the clinically relevant benefits that dual-energy computed tomography (CT) contributes over conventional single-energy CT in the emergency setting using practical imaging examples. Particular emphasis will be placed on acute gout, bone marrow edema, acute renal colic, acute cardiovascular and neurovascular emergencies aswell as characterization of abdominal incidentalomas. The relevant scientific literature will be summarized and limitations of the technique also will be emphasized to provide the reader with a rounded concept of the current state of technology.