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Extensive research in the last few decades has conclusively demonstrated the significant influence of experimental conditions, surfactants, and synthesis methods on semiconductors' properties in technological applications. Therefore, in this study, the synthesis of molybdenum oxide (MoO 3 ) was reported by the addition of 2.5 (MoO 3 _2.5), 5 (MoO 3 _5), 7.5 (MoO 3 _7.5), and 10 mL (MoO 3 _10) of nitric acid, obtaining the respective concentrations of 0.6, 1.10, 1.6, and 0.6 mol L -1 . In this study, all samples were synthesized by the hydrothermal method at 160 °C for 6 h. The materials obtained were structurally characterized by X-ray diffraction (XRD) and structural Rietveld refinement, Raman spectroscopy, and infrared spectroscopy (FTIR), confirming the presence of all crystallographic planes and bands associated with active modes for the pure hexagonal phase ( h -MoO 3 ) when the solution's concentration was 0.6 mol L -1 of nitric acid. For concentrations of 1.10, 1.60, and 2.10 mol L -1 , the presence of crystallographic planes and active modes associated with the formation of mixtures of molybdenum oxide polymorphs was confirmed, in this case, the orthorhombic, monoclinic, and hexagonal phases. X-ray photoelectron spectroscopy reveals the occurrence of the states Mo 4+ , Mo 5+ , and Mo 6+ , which confirm the predominance of the acid Lewis sites, corroborating the analysis by adsorption of pyridine followed by characterization by infrared spectroscopy. The images collected by scanning electron microscopy confirmed the information presented in the structural characterization, where microcrystals with hexagonal morphology were obtained for the MoO 3 _2.5 sample. In contrast, the MoO 3 _5, MoO 3 _7.5, and MoO 3 _10 samples exhibited hexagonal and rod-shaped microcrystals, where the latter morphology is characteristic of the orthorhombic phase. The catalytic tests carried out in the conversion of oleic acid into methyl oleate, using the synthesized samples as a heterogeneous catalyst, resulted in conversion percentages of 52.5, 58.6, 69.1, and 97.2% applying the samples MoO 3 _2.5, MoO 3 _5, MoO 3 _7.5, and MoO 3 _10, respectively. The optimization of the catalytic tests with the MoO 3 _10 sample revealed that the conversion of oleic acid into methyl oleate is a thermodynamically favorable process, with a variation in the Gibbs free energy between -67.3 kJ mol -1 and 83.4 kJ mol -1 as also, the energy value of activation of 24.6 kJ mol -1 , for the temperature range from 80 to 140 °C, that is, from 353.15 to 413.15 K, respectively. Meanwhile, the catalyst reuse tests resulted in percentages greater than 85%, even after the ninth catalytic cycle. Therefore, the expressive catalytic performance of the mixture of h -MoO 3 and α-MoO 3 (MoO 3 _10) phases is confirmed, associated with the synergistic effect, mainly due to the increase in the surface area and available Lewis sites of these phases.

Some oxysterols were shown to promote osteogenic differentiation of mesenchymal stem cells (MSCs). Little is known about the effects of 7-ketocholesterol (7-KC) in this process. We describe its impact on human adipose tissue-derived MSC (ATMSC) osteogenic differentiation. ATMSCs were incubated with 7-KC in osteogenic or adipogenic media. Osteogenic and adipogenic differentiation was evaluated by Alizarin red and Oil Red O staining, respectively. Osteogenic ( ALPL, RUNX2, BGLAP ) and adipogenic markers ( PPARƔ, C/EBPα ) were determined by RT-PCR. Differentiation signaling pathways (SHh, Smo, Gli-3, β-catenin) were determined by indirect immunofluorescence. ATMSCs treated with 7-KC in osteogenic media stained positively for Alizarin Red. 7-KC in adipogenic media decreased the number of adipocytes. 7-KC increased ALPL and RUNX2 but not BGLAP expressions. 7-KC decreased expression of PPARƔ and C/EBPα , did not change SHh, Smo, and Gli-3 expression, and increased the expression of β-catenin. In conclusion, 7-KC favors osteogenic differentiation of ATMSCs through the expression of early osteogenic genes (matrix maturation phase) by activating the Wnt/β-catenin signaling pathway, while inhibiting adipogenic differentiation. This knowledge can be potentially useful in regenerative medicine, in treatments for bone diseases.

Dye effluents cause diverse environmental problems. Methylene blue (MB) dye stands out since it is widely used in the textile industry. To reduce the pollution caused by the MB, we developed biosorbents from tucumã seeds, where the in natura seeds were treated with NaOH (BT) and H 3 PO 4 (AT) solutions and characterized by Boehm titration, point of zero charges, FTIR, TGA, BET, and SEM. It was observed that the acid groups predominate on the surface of the three biosorbents. The process was optimized for all biosorbents at pH = 8, 7.5 g/L, 240 min, C 0  = 250 mg/L, and 45 ℃. BT was more efficient in removing MB (96.20%; Q Max  = 35.71 mg/g), while IT and AT removed around 60% in similar conditions. The adsorption process best fits Langmuir and Redlich-Peterson isotherms, indicating a hybrid adsorption process (monolayer and multilayer) and pseudo-second-order kinetics. Thermodynamic data confirmed an endothermic and spontaneous adsorption process, mainly for BT. MB was also recovered through a desorption process with ethanol, allowing the BT recycling and reapplication of the dye. Thus, an efficient and sustainable biosorbent was developed, contributing to reducing environmental impacts., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Leukemias are among the most prevalent types of cancer worldwide. Bone marrow mesenchymal stem cells (MSCs) participate in the development of a suitable niche for hematopoietic stem cells, and are involved in the development of diseases such as leukemias, to a yet unknown extent. Here we described the effect of secretome of bone marrow MSCs obtained from healthy donors and from patients with acute myeloid leukemia (AML) on leukemic cell lineages, sensitive (K562) or resistant (K562-Lucena) to chemotherapy drugs. Cell proliferation, viability and death were evaluated, together with cell cycle, cytokine production and gene expression of ABC transporters and cyclins. The secretome of healthy MSCs decreased proliferation and viability of both K562 and K562-Lucena cells; moreover, an increase in apoptosis and necrosis rates was observed, together with the activation of caspase 3/7, cell cycle arrest in G0/G1 phase and changes in expression of several ABC proteins and cyclins D1 and D2. These effects were not observed using the secretome of MSCs derived from AML patients. In conclusion, the secretome of healthy MSCs have the capacity to inhibit the development of leukemia cells, at least in the studied conditions. However, MSCs from AML patients seem to have lost this capacity, and could therefore contribute to the development of leukemia.

Background: Diffuse large B-cell lymphoma (DLBCL) especially affects the older population. Old (≥60 years) and very old age (≥80 years) DLBCL patients often present high-risk molecular alterations, lower tolerability to conventional immunochemotherapy, and poor clinical outcomes. In this scenario, attenuated therapeutic strategies, such as the R-MiniCHOP and R-MiniCHOP of the elderly regimens, have emerged for this particularly fragile population. However, the responses, clinical outcomes, and toxicities of these regimens currently remain poorly understood, mainly because these individuals are not usually included in controlled clinical trials., Methods: This retrospective, observational, and single-center real-world study included 185 DLBCL, NOS patients older than 70 years treated at the largest oncology center in Latin America from 2009 to 2020. We aimed to assess the outcomes, determine survival predictors, and compare responses and toxicities between three different primary therapeutic strategies, including the conventional R-CHOP regimen and the attenuated R-MiniCHOP and R-MiniCHOP of the elderly protocols., Results: The median age at diagnosis was 75 years (70-97 years), and 58.9% were female. Comorbidities were prevalent, including 19.5% with immobility, 28.1% with malnutrition, and 24.8% with polypharmacy. Advanced clinical stage was observed in 72.4%, 48.6% had bulky disease ≥7 cm, 63.2% had B-symptoms, and 67.0% presented intermediate-high/high-risk IPI. With a median follow-up of 6.3 years, the estimated 5-year OS and PFS were 50.2% and 44.6%, respectively. The R-MiniCHOP of the elderly regimen had a lower ORR ( p = 0.040); however, patients in this group had higher rates of unfavorable clinical and laboratory findings, including hypoalbuminemia ( p = 0.001), IPI ≥ 3 ( p = 0.013), and NCCN-IPI ≥ 3 ( p = 0.002). Although associated with higher rates of severe neutropenia ( p = 0.003), the R-CHOP regimen promoted increased OS ( p = 0.003) and PFS ( p = 0.005) in comparison to the attenuated protocols. Additionally, age ≥ 75 years, high levels of LDH, B-symptoms, advanced clinical stage (III/IV), neutrophilia, and low lymphocyte/monocyte ratio were identified as poor prognostic factors in this cohort., Conclusions: In this large and real-life Latin American cohort, we demonstrated that patients with DLBCL, NOS older than 70 years still do not have satisfactory clinical outcomes in 2024, with half of cases not reaching 5 years of life expectancy after diagnosis. Although the conventional R-CHOP offers response and survival advantages over attenuated regimens, its myelotoxicity is not negligible. Therefore, the outcomes reported and the prognostic factors here identified may assist clinicians in the appropriate selection of therapeutic strategies adapted to the risk for old and very old DLBCL patients.

Background: Mantle cell lymphoma (MCL) is a rare malignancy with heterogeneous behavior. Despite the therapeutic advances recently achieved, MCL remains incurable. Currently, the standard of care for young and fit patients involves induction immunochemotherapy followed by up-front autologous stem cell transplantation (ASCT). However, the role of more intensive induction regimens, such as those based on high doses of cytarabine (HDAC), remains controversial in the management of ASCT-eligible patients., Methods: This retrospective, observational, and single-center study involved 165 MCL patients treated at the largest oncology center in Latin America from 2010 to 2022. We aimed to assess outcomes, determine survival predictors, and compare responses between different primary therapeutic strategies, with a focus on assessing the impact of HDAC-based regimens on outcomes in ASCT-eligible patients., Results: The median age at diagnosis was 65 years (38-89 years), and 73.9% were male. More than 90% of the cases had a classic nodal form (cnMCL), 76.4% had BM infiltration, and 56.4% presented splenomegaly. Bulky ≥ 7 cm, B-symptoms, ECOG ≥ 2, and advanced-stage III/IV were observed in 32.7%, 64.8%, 32.1%, and 95.8%, respectively. Sixty-four percent of patients were categorized as having high-risk MIPI. With a median follow-up of 71.1 months, the estimated 2-year OS and EFS were 64.1% and 31.8%, respectively. Patients treated with (R)-HDAC-based regimens had a higher ORR (85.9% vs. 65.7%, p = 0.007) compared to those receiving (R)-CHOP, as well as lower POD-24 rates (61.9% vs. 80.4%, p = 0.043) and lower mortality (43.9% vs. 68.6%, p = 0.004). However, intensified induction regimens with (R)-HDAC were not associated with a real OS benefit in MCL patients undergoing up-front consolidation with ASCT (2-year OS: 88.7% vs. 78.8%, p = 0.289). Up-front ASCT was independently associated with increased OS ( p < 0.001), EFS ( p = 0.005), and lower POD-24 rates ( p < 0.001) in MCL. Additionally, CNS infiltration, TLS, hypoalbuminemia, and the absence of remission after induction were predictors of poor OS., Conclusions: In the largest Latin American cohort of MCL patients, we confirmed the OS benefit promoted by up-front consolidation with ASCT in young and fit patients, regardless of the intensity of the immunochemotherapy regimen used in the pre-ASCT induction. Although HDAC-based regimens were not associated with an unequivocal increase in OS for ASCT-eligible patients, it was associated with higher ORR and lower rates of early relapses for the whole cohort.

In this study, the multi-marker approach was used for the first time with a highly urbanized lake located in the city of Fortaleza, Brazil, to provide a comprehensive view of temporal trends in sources of pollutants and evaluate the relation between the influence of anthropogenic activities and socioeconomic development. Total concentrations of the markers analyzed ranged from 21.0 to 103.8 ng g -1 , 450.2 to 2390.2 ng g -1 , and 233.8 to 9827.3 ng g -1 for ∑ PAHs , ∑ n-alk , and ∑ sterols , respectively. Concentrations and patterns of PAH, AH, and sterol ratio distribution changed over time and may be associated with different episodes in the history of the city of Fortaleza. The marker ratio distribution in the sediment core revealed an overlap of natural and anthropogenic sources, with degraded oil, biogenic inputs, pyrogenic processes, and fecal contamination from humans and animals in the past changing to petroleum fossil inputs and high contamination from sewage in the present day. The distribution of markers and the chronological history of Fortaleza revealed two distinct periods related to human activities during the development of the city. In the first period (prior to the 1950s), the main human activities were animal breeding and the use of biomass for domestic activities, public and cargo transportation, and commercial activities, especially food production. In the second period (after the 1950s), expansion of the city occurred due to the so-called Brazilian economic miracle and the main human activities were industrialization and urbanization processes, involving deforestation, paving, sewage discharge, and petroleum combustion., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Oxysterols are the products of cholesterol oxidation. They have a wide range of effects on several cells, organs, and systems in the body. Oxysterols also have an influence on the physiology of the immune system, from immune cell maturation and migration to innate and humoral immune responses. In this regard, oxysterols have been involved in several diseases that have an immune component, from autoimmune and neurodegenerative diseases to inflammatory diseases, atherosclerosis, and cancer. Here, we review data on the participation of oxysterols, mainly 25-hydroxycholesterol and 7α,25-dihydroxycholesterol, in the immune system and related diseases. The effects of these oxysterols and main oxysterol receptors, LXR and EBI2, in cells of the immune system (B cells, T cells, macrophages, dendritic cells, oligodendrocytes, and astrocytes), and in immune-related diseases, such as neurodegenerative diseases, intestinal diseases, cancer, respiratory diseases, and atherosclerosis, are discussed.

Oxysterols are oxidized derivatives of cholesterol produced by enzymatic activity or non-enzymatic pathways (auto-oxidation). The oxidation processes lead to the synthesis of about 60 different oxysterols. Several oxysterols have physiological, pathophysiological, and pharmacological activities. The effects of oxysterols on cell death processes, especially apoptosis, autophagy, necrosis, and oxiapoptophagy, as well as their action on cell proliferation, are reviewed here. These effects, also observed in several cancer cell lines, could potentially be useful in cancer treatment. The effects of oxysterols on cell differentiation are also described. Among them, the properties of stimulating the osteogenic differentiation of mesenchymal stem cells while inhibiting adipogenic differentiation may be useful in regenerative medicine.

Copper molybdate nanoplates were synthesized by a sonochemical process at room temperature, which we report as a simple and cost-effective route. Structural analysis of the material by the Rietveld method of X-ray diffraction (XRD) data revealed lindgrenite Cu 3 (MoO 4 ) 2 (OH) 2 in a single-phase structure. All the vibrational modes characteristic of the space group were identified by Raman vibrational and near-infrared (NIR) spectroscopies. The profile obtained for N 2 adsorption/desorption was type III hysteresis, characteristic of mesoporous materials, with a surface area of 70.77(1) m 2 g -1 . The micrographs of the material obtained by scanning electron microscopy showed nanoplates with nanometric sizes and an anisotropic growth aspect. The catalytic activity of lindgrenite was evaluated by esterifying oleic acid with methanol, showing high conversion rate to methyl oleate and good catalyst stability after seven recycling cycles. Above all, the best catalytic performance was reached when we optimized parameters such as oleic acid:methanol molar ratio of 1:5, 5% of catalyst dosage, and reaction time of 5 h, resulting in 98.38% of conversion at 413 K. Therefore, sonochemically synthesized lindgrenite proved to be a high potential material for biofuel production by oleic acid esterification., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Mesenchymal stem cells have the ability to differentiate into several cell types when exposed to determined substances, including oxysterols. Oxysterols are cholesterol products derived from its auto-oxidation by reactive species or from enzymatic action. They are present in the body in low quantities under physiological conditions and exhibit several physiological and pharmacological actions according to both the types of oxysterol and tissue. Some of them are cytotoxic while others have been shown to promote cell differentiation through the action on several different receptors, such as nuclear LXR receptors and Smoothened receptor ligands. Here, we review the main pathways by which oxysterols have been associated with cell differentiation and death of mesenchymal stem cells., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ferroptosis is a type of cell death that was described less than a decade ago. It is caused by the excess of free intracellular iron that leads to lipid (hydro) peroxidation. Iron is essential as a redox metal in several physiological functions. The brain is one of the organs known to be affected by iron homeostatic balance disruption. Since the 1960s, increased concentration of iron in the central nervous system has been associated with oxidative stress, oxidation of proteins and lipids, and cell death. Here, we review the main mechanisms involved in the process of ferroptosis such as lipid peroxidation, glutathione peroxidase 4 enzyme activity, and iron metabolism. Moreover, the association of ferroptosis with the pathophysiology of some neurodegenerative diseases, namely Alzheimer's, Parkinson's, and Huntington's diseases, has also been addressed.

Homogeneous catalysts used for biodiesel synthesis have several limitations, including non-recoverability/reusability, saponification, emulsification, equipment corrosion, and environmental pollution. To overcome these limitations, we synthesized a novel catalyst via calcination of pineapple leaves waste. This catalyst was characterized by X-ray powder diffraction, X-ray fluorescence, Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and soluble alkalinity measurements. The catalyst's activity with regards to soybean oil transesterification was analyzed, and multiple process parameters (temperature, catalyst amount, reaction time, and methanol:oil molar ratio) were examined. A high catalytic activity, probably related to the 85 wt% content of alkali/alkali metals (K, Ca and Mg), was observed after a 30 min reaction time, 60 °C, 4 wt% of catalyst, oil to methanol molar ratio of 1:40, reaching an oil to biodiesel conversion above 98%. We conclude that the novel catalyst presented here is efficient, cost-effective, and sustainable, while simultaneously abundant waste is reduced., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Many organic dye pollutants have been identified in rivers and lakes around the world, and concern is growing with them as they cause serious changes in the ecological balance of aquatic environments. One of these dyes is rhodamine R6G, which is very water-soluble and has a high corrosive power. Therefore, Clitoria fairchildiana (CF) pods were used as a biosorbent to remove R6G from synthetic dye effluents. CF was characterized by infrared spectroscopy, thermogravimetric analysis, x-ray diffraction, elemental analysis, Boehm titration, and zero charge point measurements. The influence of various factors, such as solution pH, contact time, adsorbent mass, and concentration of R6G, was studied using batch equilibrium experiments. The optimum contact time to reach equilibrium was found to be 15 min, while the optimum adsorbent dose was 8 g L -1 . The maximum adsorption capacity of CF (73.84 mg g -1 ) was observed at pH 6.4 and 298.15 K. Adsorption kinetics followed a pseudo-second-order law, and the isotherm could be best fitted with a Liu model. The obtained thermodynamic parameters indicate that the adsorption of R6G is spontaneous and enthalpy-driven. We thus conclude that CF is an efficient, green, and readily available biosorbent for dye removal from wastewater.

7-Ketocholesterol (7-KC) is a cholesterol oxidation product with several biological functions. 7-KC has the capacity to cause cell death depending on the concentration and specific cell type. Mesenchymal stem cells (MSCs) are multipotent cells with the ability to differentiate into various types of cells, such as osteoblasts and adipocytes, among others. MSCs contribute to the development of a suitable niche for hematopoietic stem cells, and are involved in the development of diseases, such as leukemia, to a yet unknown extent. Here, we describe the effect of 7-KC on the death of bone marrow MSCs from patients with acute myeloid leukemia (LMSCs). LMSCs were less susceptible to the death-promoting effect of 7-KC than other cell types. 7-KC exposure triggered the extrinsic pathway of apoptosis with an increase in activated caspase-8 and caspase-3 activity. Mechanisms other than caspase-dependent pathways were involved. 7-KC increased ROS generation by LMSCs, which was related to decreased cell viability. 7-KC also led to disruption of the cytoskeleton of LMSCs, increased the number of cells in S phase, and decreased the number of cells in the G1/S transition. Autophagosome accumulation was also observed. 7-KC downregulated the SHh protein in LMSCs but did not change the expression of SMO. In conclusion, oxiapoptophagy (OXIdative stress + APOPTOsis + autophagy) seems to be activated by 7-KC in LMSCs. More studies are needed to better understand the role of 7-KC in the death of LMSCs and the possible effects on the SHh pathway.

Oxysterols are 27-carbon oxidation products of cholesterol metabolism. Oxysterols possess several biological actions, including the promotion of cell death. Here, we examined the ability of 7-ketocholesterol (7-KC), cholestane-3β-5α-6β-triol (triol), and a mixture of 5α-cholestane-3β,6β-diol and 5α-cholestane-3β,6α-diol (diol) to promote cell death in a human breast cancer cell line (MDA-MB-231). We determined cell viability, after 24-h incubation with oxysterols. These oxysterols promoted apoptosis. At least part of the observed effects promoted by 7-KC and triol arose from an increase in the expression of the sonic hedgehog pathway mediator, smoothened. However, this increased expression was apparently independent of sonic hedgehog expression, which did not change. Moreover, these oxysterols led to increased expression of LXRα, which is involved in cellular cholesterol efflux, and the ATP-binding cassette transporters, ABCA1 and ABCG1. Diols did not affect these pathways. These results suggested that the sonic hedgehog and LXRα pathways might be involved in the apoptotic process promoted by 7-KC and triol.

Introduction: Alkaloids-derived drugs are a billionaire world-market and several phytochemical investigations aim the identification of new sources and/or structures. Thus, improving the way of extracting and methods to quantify them are of utmost importance., Objective: To quantify isoquinoline-derived alkaloids in Unonopsis duckei R.E. Fr. through a new validated high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method in combination with a statistical mixture design that aimed a proper direct extraction of these compounds from leaves., Methodology: Extracts were obtained with acetone, methanol, chloroform, and n-hexane in different combinations and proportions. Chemometrics were applied in order to compare peak areas, and therefore evaluate synergism and antagonism effects between the solvents. After selection of extraction solvent, the quantification was validated and applied in the best solvent combination to quantify the main alkaloids in U. duckei., Results: Chemometrics indicated a synergistic effect between chloroform and methanol solvents, thus improving alkaloid extraction and extract yield. Analytes were quantified in a 15-min method, with limits of detection (LODs) between 0.5 and 5.2 ng/mL and limits of quantification (LOQs) between 1.6 and 17.2 ng/mL. The accuracy ranged between 80 and 120%. Coefficients of variation were lower than 17.42% at all concentrations. Concentrations of the alkaloids in U. duckei varied from 6.79 to 131.10 μg/g of dried leaf and glaziovine was found to be the main compound., Conclusion: The integration of simplex centroid model and quantification by HPLC-MS/MS is promising. Statistical optimisation of the alkaloid extraction and application of selective, sensitive and robust HPLC-MS/MS method will contribute to quality control applications in phytotherapeutic medicines., (Copyright © 2018 John Wiley & Sons, Ltd.)

Background: Population seroprevalence and rates of mother-to-child transmission are important in determining the incidence of congenital toxoplasmosis. (CT) Mother-to-child transmission depends on the timing of acute maternal infection and treatment during pregnancy. The incidence of CT varies widely across geographic regions, ranging from 1 to 10 cases per 10,000 live births. The incidence of symptomatic disease varies from 0.15 to 0.34 cases per 10,000., Methods: This is a review of patients treated at a pediatric CT clinic at a university hospital in the south of Brazil, from 2004 to 2014., Results: The annual incidence of CT varied from 0 to 14 cases per 10,000 live births, with a mean incidence of 6 cases per 10,000 during the 10 years studied (CI 95%: 3.02-8.91). The incidence of symptomatic CT varied from 0 to 9 cases per 10,000 live births, with a mean incidence of 5 per 10,000 (CI 95%: 2.44-6.94). There were 5 (14.3%) asymptomatic cases. The main findings were retinochoroiditis (54%), intracranial calcifications (37.5%) and altered cerebrospinal fluid (37.5%)., Conclusions: The incidence of CT and the rate of symptomatic cases were in accordance with the previous data from other studies in Brazil, being significantly higher than in previous North American and European studies.

A number of adjuvant formulations were assayed in mice immunized with 3.75 µg of A/California/7/2009 (H1N1) pdm09 influenza vaccine with vitamins A, D and/or E in emulsions or B2 and/or B9 combined with Bordetella pertussis MPLA and/or alum as adjuvants. Squalene was used as positive control, as well as MPLA with alum. The immune response was evaluated by a panel of tests, including a hemagglutination inhibition (HAI) test, ELISA for IgG, IgG1, and IgG2a and IFN-γ, IL-2, IL-6 and IL-10 quantification in splenocyte culture supernatant after stimulus with influenza antigen. Immunological memory was evaluated using a 1/10 dose booster 60 days after the first immunization followed by assessment of the response by HAI, IgG ELISA, and determination of the antibody affinity index. The highest increases in HAI, IgG1 and IgG2a titers were obtained with the adjuvant combinations containing vitamin E, or the hydrophilic combinations containing MPLA and alum or B2 and alum. The IgG1/IgG2a ratio indicates that the response to the combination of B2 with alum would have more Th2 character than the combination of MPLA with alum. In an assay to investigate the memory response, a significant increase in HAI titer was observed with a booster vaccine dose at 60 days after immunization with vaccines containing MPLA with alum or B2 with alum. Overall, of the 27 adjuvant combinations, MPLA with alum and B2 with alum were the most promising adjuvants to be evaluated in humans.

Background: Recent publications have described significant variability in the femoral attachment and overall anatomy of the anterolateral ligament (ALL). Additionally, there is a paucity of data describing its structural properties., Purpose: Quantitative data characterizing the anatomic and radiographic locations and the structural properties of the ALL may be used to guide graft selection and placement and to facilitate the future development of an evidence-based approach to ALL reconstructions., Study Design: Descriptive laboratory study., Methods: Identification of the ALL was performed by a combined outside-in and inside-out anatomic dissection of 15 nonpaired fresh-frozen cadaveric knees. Quantitative anatomic relationships were calculated using a 3-dimensional coordinate measuring device. Measurements on anteroposterior (AP) and lateral radiographs were obtained by use of a picture archiving and communications system program. Structural properties were characterized during a single pull-to-failure test using a tensile testing machine. All anatomic, radiographic, and biomechanical measurements were reported as mean values and 95% CIs., Results: The ALL was identified as a thickening of the lateral capsule coming under tension with an applied internal rotation at 30° of flexion. Its femoral attachment was located 4.7 mm (95% CI, 3.5-5.9 mm) posterior and proximal to the fibular collateral ligament attachment and coursed anterodistally to its anterolateral tibial attachment approximately midway between the center of the Gerdy tubercle and the anterior margin of the fibular head; the tibial attachment was located 24.7 mm (95% CI, 23.3-26.2 mm) and 26.1 mm (95% CI, 23.9-28.3 mm) from each structure, respectively. On the AP radiographic view, the ALL originated on the femur 22.3 mm (95% CI, 20.7-23.9 mm) proximal to the joint line and inserted on the tibia 13.1 mm (95% CI, 12.3-13.9 mm) distal to the lateral tibial plateau. On the lateral view, the femoral attachment was 8.4 mm (95% CI, 6.8-10.0 mm) posterior and proximal to the lateral epicondyle. The tibial attachment was 19.0 mm (95% CI, 17.1-20.9 mm) posterior and superior to the center of the Gerdy tubercle. The mean maximum load was 175 N (95% CI, 139-211 N) and the stiffness was 20 N/mm (95% CI, 16-25 N/mm). Failure occurred by 4 distinct mechanisms: ligamentous tear at the femoral (n = 4) or tibial (n = 1) attachment, midsubstance tear (n = 4), and bony avulsion of the tibial attachment (Segond fracture; n = 6)., Conclusion: Defined ALL attachment locations can be reproducibly identified with intraoperative landmarks or radiographs. The biomechanical analysis suggests that most traditional soft tissue grafts are sufficient for ALL reconstruction., Clinical Relevance: The ALL was consistently found in all knees. Segond fractures appear to occur primarily from the avulsion of the ALL., (© 2015 The Author(s).)

Gait variability is related to functional decline in the elderly. The dual-task Timed Up and Go Test (TUG-DT) reflects the performance in daily activities. Objective To evaluate the differences in time to perform the TUG with and without DT in elderly women with different ages and levels of education and physical activity. Method Ninety-two elderly women perfomed the TUG at usual and fast speeds, with and without motor and cognitive DT. Results Increases in the time to perform the TUG-DT were observed at older ages and lower educational levels, but not at different levels of physical activity. More educated women performed the test faster with and without DT at both speeds. When age was considered, significant differences were found only for the TUG-DT at both speeds. Conclusion Younger women with higher education levels demonstrated better performances on the TUG-DT.