Characterization of Green Synthesized Nanoparticles with Anti-diabetic Properties. A Systematic Review.

BACKGROUND: Plants are used in medicine because they are low-cost, widely available, and have few side effects (compared to pharmacological treatment). Plants have phytocompounds with antidiabetic properties that can be delivered using nanoparticles (NPs). OBJECTIVE: To describe the antidiabetic properties of green synthesized NPs (GSNPs) and their characterization methods. METHODS: Three databases were searched using the terms "type 2 diabetes mellitus," "antidiabetic effects," "phytochemicals," "plants," and "nanoparticles." Studies describing the antidiabetic effects (in vitro or animal models) of NPs synthesized by plant extracts and characterizing them through UV-Vis spectroscopy, FTIR, XRD, SEM, TEM, and DLS were included. RESULTS: 16 studies were included. In vitro studies reported enzyme inhibition values between 11% (H. polyrhizus) and 100% (A. concinna) for alfa-amylase and between 41.1% (M. zapota) and 100% (A. concinna) for alfa-glucosidase. Animal studies with Wistar Albino rats having diabetes (induced by alloxan or streptozotocin) reported improved blood glucose, triglycerides, total cholesterol, LDL, and HDL after treatment with GSNPs. Regarding characterization, NP sizes were measured with DLS (25-181.5 nm), SEM (52.1-91 nm), and TEM (8.7-40.6 nm). The surface charge was analyzed with zeta potential (-30.7 to -2.9 mV). UV-Vis spectroscopy was employed to confirm the formations of AgNPs (360-460 nm), AuNPs (524-540 nm), and ZnONPs (300-400 nm), and FTIR was used to identify plant extract functional groups. CONCLUSIONS: GSNP characterization (shape, size, zeta potential, and others) is essential to know the viability and stability, which are important to achieve health benefits for biomedical applications. Studies reported good enzyme inhibition percentages in in vitro studies, decreasing blood glucose levels and improving lipid profiles in animal models with diabetes. However, these studies had limitations in the methodology and potential risk of bias, so results need careful interpretation.

Immune response to neurotoxic South American snake venoms.

South American rattlesnakes (Crotalus durissus spp) and coral snakes (Micrurus sp) venoms are characterized by inducing a limited inflammatory innate immune response, in contrast to Bothrops sp snake venoms which exert a prominent inflammatory activity. Some Crotalus durissus spp venoms, in addition, exert immunosuppressive activities that hamper the development of neutralizing antibodies in animals immunized for antivenom production. Micrurus sp venoms are rich in low molecular mass neurotoxins that elicit a limited immune response. These characteristics make it difficult to generate antivenoms of high neutralizing activity. Therefore, the study of the mechanisms operating behind this limited immune response to venoms is relevant from both fundamental and practical perspectives. This review summarizes key aspects of the immune response to these venoms and discusses some pending challenges to further understand these phenomena and to improve antivenom production.

Propylene Glycol Potentiates the Inhibitory Action of CTZ Paste on Antibiotic-Resistant Enterococcus faecalis Isolated from the Root Canal: An In Vitro Study.

This study aimed to evaluate if the change of vehicle for CTZ (Chloramphenicol, Tetracycline, zinc oxide, and Eugenol) paste improves the inhibition of Enterococcus faecalis in vitro. The vehicles evaluated alone and mixed with CTZ were Eugenol, propylene glycol (PG), super-oxidized solution (SOS), grapefruit-seed extract (GSE), and 0.9% saline solution as a negative control. A clinical isolate of E. faecalis was morphologically and biochemically characterized, and its antimicrobial susceptibility was tested using 20 antimicrobial agents. Once characterized, the clinical isolate was cultivated to perform the Kirby-Bauer disc diffusion method with paper discs embedded with the different vehicles mixed or used alone, and incubated at 37 °C for 24 h. Data were analyzed using one-way ANOVA, and the means were compared using Tukey test with a significance level of p < 0.05. For vehicles used alone, GSE presented the greatest inhibition showing a statistically significant difference with the rest of the vehicles. When vehicles were mixed with the CTZ paste, PG showed a greater inhibition with a statistically significant difference from the rest of the vehicles. In conclusion, the vehicle used to mix the CTZ paste plays an important role in the inhibition of E. faecalis in vitro; therefore, we consider that this can be an important factor to achieve success in the use of this technique.

Hydrologic-hydraulic assessment of SUDS control capacity using different modeling approaches: a case study in Bogotá, Colombia.

Urban flooding has increased in response to impervious surface intensification, the loss of green areas, and high-intensity rainfall associated with climate change. Sustainable urban drainage systems (SUDS) are an appealing option for stormwater management; however, their hydraulic control capabilities have received little attention. We developed a comparative model-based approach with 24 scenarios to contrast the hydrologic and hydraulic response of a highly discretized (HD) 1D model and a coupled 1D-2D model, considering the impact of rainwater harvesting systems and tree pits. An additional scenario was modeled including attenuation storage tanks, green roofs, and pervious pavements. A heavily urbanized flood-prone catchment with severe land-use constraints in Bogotá, Colombia, was selected for analysis. The findings revealed that SUDS can contribute to reducing the number of flooded junctions, overloaded conduits' length, overloading time, nodal inundation depth, and waterlogging extent. Furthermore, the HD 1D model can reproduce the coupled 1D-2D model results in terms of hydrologic response and some hydraulic control indicators. Further research is needed for an accurate description of the internal hydraulic mechanisms of SUDS interacting with overland flow. The key findings of this study provide model-based evidence to support urban stormwater management decision-making in data-scarce environments.

Anti-Neuroinflammatory Potential of a Nectandra angustifolia (Laurel Amarillo) Ethanolic Extract.

Microglia, the resident macrophage-like population in the CNS, plays an important role in the pathogenesis of many neurodegenerative disorders. Nectandra genus is known to produce different metabolites with anti-inflammatory, anti-oxidant and analgesic properties. Although the species Nectandra angustifolia is popularly used for the treatment of different types of inflammatory processes, its biological effects on neuroinflammation have not yet been addressed. In this study, we have investigated the role of a Nectandra angustifolia ethanolic extract (NaE) in lipopolysaccharide (LPS)-induced neuroinflammation in vitro and in vivo. In LPS-activated BV2 microglial cells, NaE significantly reduced the induced proinflammatory mediators TNF-α, IL-1ß, IL-6, COX-2 and iNOS, as well as NO accumulation, while it promoted IL-10 secretion and YM-1 expression. Likewise, reduced CD14 expression levels were detected in microglial cells in the NaE+LPS group. NaE also attenuated LPS-induced ROS and lipid peroxidation build-up in BV2 cells. Mechanistically, NaE prevented NF-κB and MAPKs phosphorylation, as well as NLRP3 upregulation when added before LPS stimulation, although it did not affect the level of some proteins related to antioxidant defense such as Keap-1 and HO-1. Additionally, we observed that NaE modulated some activated microglia functions, decreasing cell migration, without affecting their phagocytic capabilities. In LPS-injected mice, NaE pre-treatment markedly suppressed the up-regulated TNF-α, IL-6 and IL-1ß mRNA expression induced by LPS in brain. Our findings indicate that NaE is beneficial in preventing the neuroinflammatory response both in vivo and in vitro. NaE may regulate microglia homeostasis, not only restraining activation of LPS towards the M1 phenotype but promoting an M2 phenotype.

Differences in erythrocytes size and shape in prediabetes and diabetes assessed by two microscopy techniques and its association with dietary patterns. Pilot study.

Hemorheology and microcirculation alterations are caused by erythrocyte size and shape (ESS) modifications. People´s diets can alter erythrocyte functions and membrane fluidity by changing cell membrane components. The aim was to identify differences in ESS obtained by scanning electron (SEM) and atomic force microscopy (AFM) in people with prediabetes and type 2 diabetes (T2DM) and assess their relationship with dietary patterns. The study population included 31 participants (14 healthy, 11 with prediabetes, and 6 with T2DM). Dietary intake was assessed by a food frequency questionnaire, and dietary patterns were obtained using principal component analysis. ESS (diameter, height, axial ratio, thickness, and concave depth) were obtained by SEM and AFM. Differences in ESS between groups were observed with SEM (height) and AFM (height, axial ratio, and concave depth). T2DM presented smaller erythrocytes, more elongated and more altered forms. Two dietary patterns were identified: (1) Unhealthy: more refined cereals, high-fat dairy, fast food, sugary beverages, and fewer fruits, fish, seafood, low-fat dairy, and water. (2) Prudent: higher consumption of refined cereals, vegetables, poultry, low-fat dairy and nuts, and lower tortillas, eggs, high-fat dairy, and legumes. Tertile 3 of the Unhealthy dietary pattern had 80% of healthy participants. A difference in diameter and height (0.44 and 0.32 µm, respectively) obtained by SEM was observed when comparing tertile 2 (smaller erythrocytes) versus tertile 3 in the Unhealthy dietary pattern. SEM and AFM are excellent tools to assess ESS. Unhealthy dietary patterns might be associated with altered ESS. HIGHLIGHTS: SEM and AFM are excellent tools to assess erythrocyte size and shape modifications. Two dietary patterns were identified: healthy and prudent. Smaller erythrocytes were observed in the second tertile of the unhealthy pattern.

Noninvasive Glucose Measurements Through Transcutaneous Raman Spectroscopy: A Review.

BACKGROUND: People living with diabetes need constant glucose monitoring to avoid health complications. However, they do not monitor their glucose levels as often as recommended, probably because glucose measurement devices can be painful, costly, need testing strips or sensors, require lancing the finger or inserting a sensor with risk of infection, and can be inaccurate or have failures. Therefore, developing new alternatives for noninvasive glucose measurements that overcome these disadvantages is necessary, being Raman spectroscopy (RS) a solution. OBJECTIVE: This review aims to provide an overview of the current glucose-monitoring technologies and the uses and advantages of RS to improve noninvasive transcutaneously glucose-monitoring devices. RESULTS: The skin has been used to assess glucose levels noninvasively because it is an accessible tissue where glucose can be measured in the interstitial fluid (ISF) in the epidermis (especially in the stratum corneum). The most selected skin sites to apply RS for noninvasive glucose measurements were the nailfold, finger, and forearm because, in these sites, the penetration depth of the excitation light can reach the stratum corneum (10-20 µm) and the ISF. Studies found that RS is a good optical technique to measure glucose noninvasively by comparing glucose levels obtained by RS with those from invasive methods such as glucose meters with testing strips during an oral glucose tolerance test (OGTT). CONCLUSIONS: New alternatives for noninvasive glucose measurements that overcome the disadvantages of current devices is necessary, and RS is a possible solution. However, more research is needed to evaluate the stability, accuracy, costs, and acceptance.

Anti-Adherence and Antimicrobial Activities of Silver Nanoparticles against Serotypes C and K of Streptococcus mutans on Orthodontic Appliances.

Background and Objectives: Streptococcus mutans (S. mutans) is the main microorganism associated with the presence of dental caries and specific serotypes of this bacteria have been related to several systemic diseases limiting general health. In orthodontics, white spot lesions (WSL), represent a great challenge for clinicians due to the great fluctuation of their prevalence and incidence during conventional orthodontic treatments. Although silver nanoparticles (AgNP) have been demonstrated to have great antimicrobial properties in several microorganisms, including S. mutans bacteria, there is no available information about anti adherence and antimicrobial properties of AgNP exposed to two of the most relevant serotypes of S. mutans adhered on orthodontic materials used for conventional therapeutics. The objective of this study was to determine anti-adherence and antimicrobial levels of AgNP against serotypes c and k of S. mutans on conventional orthodontic appliances. Materials and Methods: An AgNP solution was prepared and characterized using dispersion light scattering (DLS) and transmission electron microscopy (TEM). Antimicrobial and anti-adherence activities of AgNP were determined using minimal inhibitory concentrations (MIC) and bacterial adherence testing against serotypes c and k of S. mutans clinically isolated and confirmed by PCR assay. Results: The prepared AgNP had spherical shapes with a good size distribution (29.3 ± 0.7 nm) with negative and well-defined electrical charges (−36.5 ± 5.7 mV). AgNP had good bacterial growth (55.7 ± 19.3 µg/mL for serotype c, and 111.4 ± 38.6 µg/mL for serotype k) and adherence inhibitions for all bacterial strains and orthodontic wires (p < 0.05). The serotype k showed statistically the highest microbial adherence (p < 0.05). The SS wires promoted more bacterial adhesion (149.0 ± 253.6 UFC/mL × 104) than CuNiTi (3.3 ± 6.0 UFC/mL × 104) and NiTi (101.1 ± 108.5 UFC/mL × 104) arches. SEM analysis suggests CuNiTi wires demonstrated better topographical conditions for bacterial adherence while AFM evaluation determined cell wall irregularities in bacterial cells exposed to AgNP. Conclusions: This study suggests the widespread use of AgNP as a potential anti-adherent and antimicrobial agent for the prevention of WSL during conventional orthodontic therapies and, collaterally, other systemic diseases.

Actinomyces in the mediastinum. Surprise is key in all art.

Introduction: Actinomycosis is an unusual chronic granulomatous infectious disease. They are commensals in various sites of the human body but with little pathogenicity. Actinomyces israelii is the most prevalent species but more than 30 species have been described. Infection of the lower respiratory tract is unusual, the involvement of mediastinum being even rarer. Case report: A 63-year-old man, previously healthy and living in a rural area, presented with a 5-month history of hemoptysis, pleuritic pain, weight loss, and night sweats. Community-acquired pneumonia with a mediastinal mass was documented, for which he received antibiotic management. Thoracoscopy was carried out for diagnosis and resection of the mediastinal mass due to inconclusive findings in the percutaneous biopsy. Pathology reported the presence of filamentous Gram-positive bacteria visible in Grocott staining. Due to the pathology findings, and the fact that no other infectious agents were identified, a diagnosis of actinomycosis was established. Treatment with oral amoxicillin 1g TID for 6 months was initiated. Conclusions: As far as we are aware, we present the sixth case of mediastinal actinomycosis. We present this case to bring attention to this rare but clinically relevant presentation to be considered as a differential diagnosis of mediastinal masses and to emphasize the need for specific anaerobic cultures to improve the diagnostic yield.

Quinoa (Chenopodium quinoa Wild.) Seed Yield and Efficiency in Soils Deficient of Nitrogen in the Bolivian Altiplano: An Analytical Review.

Quinoa is a strategic crop due to its high N content and its adaptability to adverse conditions, where most of the soils are deficient of nitrogen (N). The central question in this review was the following: How can quinoa yield low levels of nitrogen in the soils of Altiplano? This question was unraveled based on different factors: (1) fertilization effect on productivity, (2) fertilization limits, (3) uptake and assimilation of nitrogen parameters, (4) monoculture practice effect, and (5) possible sources and strategies. One hundred eleven articles of different scientific platforms were revised and data were collected. Information from articles was used to calculate the partial factor productivity for nitrogen (PFPN), the apparent use efficiency of N (APUEN), available nitrogen (AN), and nitrogen content harvested in grains (HarvN). Quinoa responds positively to fertilization, but differences in yield were found among irrigated and rainfed conditions. Quinoa can produce 1850 kg grains ha-1 with 50 kg N ha-1 under irrigated conditions, and 670 kg grains ha-1 with 15 kg N ha-1 in rainfed conditions. Quinoa increases seed yield and HarvN increases N fertilization, but decreases nitrogen efficiency. In Altiplano, without nitrogen fertilizer, the quinoa yield relies on between 500 and 1000 kg ha-1, which shows that in the soil, there are other nitrogen sources.

Mode I Crack Propagation Experimental Analysis of Adhesive Bonded Joints Comprising Glass Fibre Composite Material under Impact and Constant Amplitude Fatigue Loading.

The T-90 Calima is a low-wing monoplane aircraft. Its structure is mainly composed of different components of composite materials, which are mainly bonded by using adhesive joints of different thicknesses. The T-90 Calima is a trainer aircraft; thus, adverse operating conditions such as hard landings, which cause impact loads, may affect the structural integrity of aircrafts. As a result, in this study, the mode I crack propagation rate of a typical adhesive joint of the aircraft is estimated under impact and constant amplitude fatigue loading. To this end, effects of adhesive thickness on the mechanical performance of the joint under quasistatic loading conditions, impact and constant amplitude fatigue in double cantilever beam (DCB) specimens are experimentally investigated. Cyclic impact is induced using a drop-weight impact testing machine to obtain the crack propagation rate (da/dN) as a function of the maximum strain energy release rate (GImax) diagram; likewise, this diagram is also obtained under constant amplitude fatigue, and both diagrams are compared to determine the effect of each type of loading on the structural integrity of the joint. Results reveal that the crack propagation rate under impact fatigue is three orders of magnitude greater than that under constant amplitude fatigue.

The Hypoxic Microenvironment Induces Stearoyl-CoA Desaturase-1 Overexpression and Lipidomic Profile Changes in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma (RCC). It is characterized by a high cell proliferation and the ability to store lipids. Previous studies have demonstrated the overexpression of enzymes associated with lipid metabolism, including stearoyl-CoA desaturase-1 (SCD-1), which increases the concentration of unsaturated fatty acids in tumor cells. In this work, we studied the expression of SCD-1 in primary ccRCC tumors, as well as in cell lines, to determine its influence on the tumor lipid composition and its role in cell proliferation. The lipidomic analyses of patient tumors showed that oleic acid (18:1n-9) is one of the major fatty acids, and it is particularly abundant in the neutral lipid fraction of the tumor core. Using a ccRCC cell line model and in vitro-generated chemical hypoxia, we show that SCD-1 is highly upregulated (up to 200-fold), and this causes an increase in the cellular level of 18:1n-9, which, in turn, accumulates in the neutral lipid fraction. The pharmacological inhibition of SCD-1 blocks 18:1n-9 synthesis and compromises the proliferation. The addition of exogenous 18:1n-9 to the cells reverses the effects of SCD-1 inhibition on cell proliferation. These data reinforce the role of SCD-1 as a possible therapeutic target.

Associations between fecal cortisol and biparental care in a pair-living primate.

OBJECTIVES: We quantified variation in fecal cortisol across reproductive periods in Azara's owl monkeys (Aotus azarae) to examine physiological mechanisms that may facilitate biparental care. Specifically, we evaluated evidence for the explanation that owl monkeys have hormonal mechanisms to mobilize energy during periods when each sex is investing heavily in reproduction, that is, the gestation period for females and the infant care period for males. MATERIALS AND METHODS: Between 2011 and 2015, we monitored 10 groups of Azara's owl monkeys from a wild population in Formosa, Argentina and collected fecal samples from 26 adults (13 males, 13 females). Using enzyme-linked immunosorbent assays, we quantified fecal cortisol as a proxy for evaluating stress responses, including energetic demands, on both sexes during periods of reproduction and parental care. RESULTS: Male cortisol was lowest during periods when they were caring for young infants (<3 months) compared with periods with older infants or no infant. Female cortisol was elevated during gestation compared with other periods. Mean fecal cortisol in both males and females was lower when an infant was present compared with when females were gestating. DISCUSSION: Our results do not support the hypothesis that owl monkey males have elevated fecal cortisol during periods when they need to mobilize energy to provide intensive infant care. Our findings are also inconsistent with the Maternal Relief hypothesis. However, results from studies measuring fecal cortisol must be interpreted with care and alternative explanations, such as seasonal fluctuations in diet and thermoenergic demands, should be considered when drawing conclusions.

How Does Mechanical Pearling Affect Quinoa Nutrients and Saponin Contents?

Agriculture is facing many challenges, such as climate change, drought, and salinity, which call for urgent interventions for fast adaptation and crop diversification. The introduction of high-value and stress tolerant crops such as quinoa would be a judicious solution to overcome constraints related to abiotic stress and to increase land productivity and farmers' incomes. The implementation of quinoa in Morocco has not been supported by a full valorization program to control the quality of quinoa seeds. The novelty of this work is to assess the pearling operation as an efficient method of saponins removal as well as the determination of total residual saponins. This study aimed to evaluate the effects of several pearling durations on nutrient and saponin content of quinoa seeds of three tested varieties (Puno, Titicaca, and ICBA-Q5). Five pearling durations were tested (0, 2, 4, 6, 7, and 8 min) using a locally manufactured pearling machine. The results indicated that a pearling duration of two minutes was enough to reduce total saponin content from 0.49% to 0.09% for Puno variety, from 0.37% to 0.07% for Titicaca variety, and from 0.57% to 0.1% for ICBA-Q5 variety. Our results showed that pearling slightly reduced protein, total fat, and moisture contents for all varieties except for Puno, where total fat content slightly increased with the pearling. Puno variety had the highest seed content in terms of protein and total fat; the ICBA-Q5 variety had the lowest. Titicaca had the highest bran content in terms of protein and total fat, ICBA-Q5 had the highest bran content in terms of ash and the lowest bran content in terms of protein and total fat, and Puno had the lowest bran content in terms of ash. Pearling had no significant effect on macronutrient contents in the processed seed, but it resulted in a very highly significant difference for most of them in the bran except for Mg and S. Regarding seed content in terms of micro-nutrients, statistical analysis showed significant differences between varieties in terms of Zn, Cu, and Mn contents, but no significant difference was recorded for Fe or B. Pearling had no significant effect on seed micronutrient contents. Therefore, to retain maximum nutritional content in the quinoa and maintain quinoa integrity, it is necessary to limit the pearling duration of quinoa to two minutes, which is enough to reduce saponin content below the Codex Standard threshold (0.12%).

Anti-inflammatory activity of Nectandra angustifolia (Laurel Amarillo) ethanolic extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Nectandra angustifolia belongs to the Lauraceae family and it is widely known in phytomedicine by local inhabitants of South America against various maladies. It is popularly used for the treatment of different types of inflammatory processes, like rheumatism, arthritis and its associated pain. AIM OF THE STUDY: To characterize the phytochemicals in an ethanolic extract of Nectandra angustifolia and to evaluate the total antioxidant content and its anti-inflammatory effect with multiparametric analyses through in vitro assays and an in vivo model. METHODS: Leaves and stems of Nectandra angustifolia were air-dried and an ethanolic extract (NaE) was further obtained. Total phenolic, flavonoid and tannin content were determined and the antioxidant activity was addressed by DPPH and FRAP assays. NaE was first analyzed by HPLC and then two tests were carried out as screening assays for anti-inflammatory activities: red blood cell membrane stabilization and protein denaturation. The non-cytotoxic concentration of NaE was determined for in vitro biological assays using RAW 264.7 (murine macrophages) cell cultures through cell counting with Trypan-blue and XTT assay. Subsequently, the cell cycle of RAW 264.7 cells exposed for 24 h to NaE was analyzed. Additionally, the anti-inflammatory capacity of NaE was evaluated by RT-qPCR of pro-inflammatory cytokines. Furthermore, NF-κB translocation was observed by confocal microscopy at different times. Finally, formalin-induced mice paw inflammation was used as an in vivo model. RESULTS: The chromatographic profile of NaE showed peaks compatible with flavonoids content. NaE exhibited better membrane stabilization effect on HRBC and protection of BSA denaturation than the standard drug (diclofenac). NaE diminished mRNA levels of pro-inflammatory cytokines when added 1-h prior LPS stimulation. Moreover, NaE prevented the translocation of NF-κB to the nucleus and in formalin-induced mice paw inflammation, reduced the edema and the stimulus of inflammatory phase. CONCLUSION: This study shows for the first time, that Nectandra angustifolia ethanolic extract has a high content of flavonoids and that possess antioxidant and anti-inflammatory biological properties as demonstrated by multiparametric analyses from in vitro assays and an in vivo model of inflammation.

Corrigendum to "In Vitro Determination of Genotoxicity Induced by Brackets Alloys in Cultures of Human Gingival Fibroblasts".

[This corrects the article DOI: 10.1155/2020/1467456.].

Whole blood can be used as an alternative to isolated peripheral blood mononuclear cells to measure in vitro specific T-cell responses in human samples.

Vaccinology is confronted with diseases for which the control of T-cell responses by the vaccine is essential. Among the assays that have been designed to assess T-cell responses, intracellular cytokine staining (ICS) combined with flow cytometry is well-suited in the frame of clinical trials. This assay can be used starting from isolated peripheral blood mononuclear cells (PBMC) or from whole blood (WB), but firm equivalence between the two sample preparation methods has yet to be established. Therefore, we compared both methods by analyzing the frequency of antigen-specific CD4+ T cells expressing at least two of four immune markers in human samples taken from two independent clinical trials (NCT00397943 and NCT00805389) with a qualified ICS assay. In the first study, M72-specific CD4+ T-cell responses were analyzed using WB-ICS and PBMC-ICS in 293 samples. Of these, 128 were double positive (value ≥ lower limit of quantification [LLOQ] with both methods), 130 were double negative and only 35 sample results were discordant, leading to an overall agreement of 88.05%. When analyzing the 128 double positive samples, it was found that the geometric mean of ratios (GMR) for paired observations was 0.98, which indicates a very good alignment between the two methods. The Deming regression fitted between the methods also showed a good correlation with an estimated slope being 1.1085. In the second study, HBsAg-specific CD4+ T-cell responses were analyzed in 371 samples. Of these, 100 were double positive, 195 were double negative and 76 sample results were discordant, leading to an overall agreement of 79.51%. The GMR for paired observations was equal to 1.20, caused by a trend for overestimation in favor of the WB samples in the very high frequencies. The estimated slope of the Deming regression was 1.3057. In conclusion, we demonstrated that WB and PBMC methods of sample collection led to statistically concordant ICS results, indicating that WB-ICS is a suitable alternative to PBMC-ICS to analyze clinical trial samples.

Application of atomic force microscopy to assess erythrocytes morphology in early stages of diabetes. A pilot study.

The study aim was to assess the application of atomic force microscopy (AFM) to evaluate erythrocyte morphology in early stages of type 2 diabetes mellitus, and the association with biochemical, anthropometric, diet, and physical activity indicators. This was a pilot cross-sectional study with four groups: healthy individuals, people with prediabetes (PDG), metabolic syndrome (MSG), and diabetes mellitus group (DMG). Blood samples were obtained to assess the erythrocyte morphology and biochemical parameters. Anthropometrical measurements were taken. Besides, a diet and a physical activity questionnaire were applied. The evaluation of the erythrocyte morphology through the AFM showed quantitative and qualitative alterations in the cell's form and size. Compared to the healthy group, the PDG had a reduction in height (-0.80 µm, p < 0.05), and an increase in axial ratio (-0.09 µm, p < 0.05); the MSG had lower concave depth (-0.19 µm, p < 0.05); and the DMG had a decreased height (-0.46 µm, p < 0.05) and concave depth (-0.29 µm, p < 0.05), and higher axial ratio (+0.08 µm) and thickness (+0.32 µm, p < 0.05). The PDG vs. DMG had a statistically significant difference in concave depth (+0.23 µm, p < 0.05) and thickness (-0.26 µm, p < 0.05). The MSG was different than the DMG in variables like axial ratio (-0.05 µm) and thickness (-0.25 µm). Besides, higher values of age, HbA1c, triglycerides, body mass index, waist-to-hip ratio, and physical inactivity were associated with altered erythrocyte morphology. AFM is a promising instrument to assess early but subtle changes in erythrocyte morphology (height, axial ratio, concave depth, thickness) before significant pathological conditions, such as type 2 diabetes mellitus. HbA1c might have a major effect in altered morphology, vs. metabolic parameters like high triglycerides, body mass index, waist, and physical inactivity.

Data for a meta-analysis of the adaptive layer in adaptive large neighborhood search.

Meta-analysis, a systematic statistical examination that combines the results of several independent studies, has the potential of obtaining problem- and implementation-independent knowledge and understanding of metaheuristic algorithms, but has not yet been applied in the domain of operations research. To illustrate the procedure, we carried out a meta-analysis of the adaptive layer in adaptive large neighborhood search (ALNS). Although ALNS has been widely used to solve a broad range of problems, it has not yet been established whether or not adaptiveness actually contributes to the performance of an ALNS algorithm. A total of 134 studies were identified through Google Scholar or personal e-mail correspondence with researchers in the domain, 63 of which fit a set of predefined eligibility criteria. The results for 25 different implementations of ALNS solving a variety of problems were collected and analyzed using a random effects model. This dataset contains a detailed comparison of ALNS with the non-adaptive variant per study and per instance, together with the meta-analysis summary results. The data enable to replicate the analysis, to evaluate the algorithms using other metrics, to revisit the importance of ALNS adaptive layer if results from more studies become available, or to simply consult the ready-to-use formulas in the summary file to carry out a meta-analysis of any research question. The individual studies, the meta-analysis and its results are described and interpreted in detail in Renata Turkes, Kenneth Sörensen, Lars Magnus Hvattum, Meta-analysis of Metaheuristics: Quantifying the Effect of Adaptiveness in Adaptive Large Neighborhood Search, in the European Journal of Operational Research.

Multidrug resistance protein 4 (MRP4/ABCC4) is overexpressed in clear cell renal cell carcinoma (ccRCC) and is essential to regulate cell proliferation.

Kidney cancer accounts for 2.5% of all cancers, with an annual global incidence of almost 300,000 cases leading to 111,000 deaths. Approximately 85% of kidney tumors are renal cell carcinoma (RCC) and their major histologic subtype is clear cell renal cell carcinoma (ccRCC). Although new therapeutic treatments are being designed and applied based on the combination of tyrosine kinase inhibitors and immunotherapy, no major impact on the mortality has been reported so far. MRP4 is a pump efflux that transporters multiple endogenous and exogenous substances. Recently it has been associated with tumoral persistence and cell proliferation in several types of cancer including pancreas, lung, ovary, colon, ostesarcoma, etc. Herein, we demonstrate for the first time, that MRP4 is overexpressed in ccRCC tumors, compared to control renal tissues. In addition, using cell culture models, we observed that MRP4 pharmacological inhibition produces an imbalance in cAMP metabolism, induces cell arrest, changes in lipid composition, increase in cytoplasmic lipid droplets and finally apoptosis. These data provide solid evidence for the future evaluation of MRP4 as a possible new therapeutic target in ccRCC.