This controlled randomized single-blind study evaluated the effects of cognitive training (CT), compared to active music therapy (AMT) and neuroeducation (NE), on initiative in patients with mild to ...moderate Alzheimer’s disease (AD). Secondarily, we explored the effects of CT on episodic memory, mood, and social relationships. Thirty-nine AD patients were randomly assigned to CT, AMT, or NE. Each treatment lasted 3 months. Before, at the end, and 3 months after treatment, neuropsychological tests and self-rated scales assessed initiative, episodic memory, depression, anxiety, and social relationships. At the end of the CT, initiative significantly improved, whereas, at the end of AMT and NE, it was unchanged. Episodic memory showed no changes at the end of CT or AMT and a worsening after NE. The rates of the patients with clinically significant improvement of initiative were greater after CT (about 62%) than after AMT (about 8%) or NE (none). At the 3-month follow-up, initiative and episodic memory declined in all patients. Mood and social relationships improved in the three groups, with greater changes after AMT or NE. In patients with mild to moderate AD, CT can improve initiative and stabilize memory, while the non-cognitive treatments can ameliorate the psychosocial aspects. The combining of CT and non-cognitive treatments may have useful clinical implications.
Recent phase III clinical trials have established the superiority of the anti-PD-1 antibodies pembrolizumab and nivolumab over the anti-CTLA-4 antibody ipilimumab in the first-line treatment of ...patients with advanced melanoma. Ipilimumab will be considered for second-line treatment after the failure of anti-PD-1 therapy.
We retrospectively identified a cohort of 40 patients with metastatic melanoma who received single-agent anti-PD-1 therapy with pembrolizumab or nivolumab and were treated on progression with ipilimumab at a dose of 3 mg kg(-1) for a maximum of four doses.
Ten percent of patients achieved an objective response to ipilimumab, and an additional 8% experienced prolonged (>6 months) stable disease. Thirty-five percent of patients developed grade 3-5 immune-related toxicity associated with ipilimumab therapy. The most common high-grade immune-related toxicity was diarrhoea. Three patients (7%) developed grade 3-5 pneumonitis leading to death in one patient.
Ipilimumab therapy can induce responses in patients who fail the anti-PD-1 therapy with response rates comparable to previous reports. There appears to be an increased frequency of high-grade immune-related adverse events including pneumonitis that warrants close surveillance.
The objective was to evaluate the effect of the use of a non-forage diet in feeding finished sheep in a feedlot regarding intake, nutrient digestibility, performance, ingestive behavior, and cost ...analysis with feed. The experiment was performed in a completely randomized complete block, with two treatments and eight blocks per treatment. The treatments were the control diet (30 of hay and 70% of concentrate, dry matter (DM) basis, normally used in the finishing system in Brazil) and the non-forage diet (100% concentrate). Animals fed non-forage diets had lower nutrient intake and metabolizable energy (ME) intake. Even though the animals that received a non-forage diet presented lower intake of DM, organic matter (OM), and crude protein (CP), there was no effect (p < 0.05) for the digestibility coefficients of these variables between diets. The time spent in rumination, total chewing, and idleness also decreased (p < 0.05) when lambs were fed a non-forage diet, due to the decreased DM intake. The profit margin value of US$10.395/animal reached by sheep fed the control diet was higher than the profit margin obtained by sheep that received the non-forage diet (US$−3.974/animal). The non-forage (pelleted) diet led to lower bio-economic performance, and its exclusive use in sheep finishing is not recommended.
The objective of this study was to evaluate the effects of partial replacement of soybean oil by fish oil on dry matter intake (DMI), growth, carcass characteristics, and meat fatty acid profile of ...feedlot lambs. Fifty Santa Ines male lambs with 17.1±2.8 of initial body weight (BW) were individually penned and used in a randomized complete block design with 10 blocks and 5 treatments. Dietary treatments, dry matter (DM) basis, consisted of: (1) control diet (CONT) with a 10:90 of forage to concentrate ratio, (2) control diet supplemented with 40g/kg of soybean oil (0FO), (3) control diet supplemented with 2.5g/kg of fish oil blend+37.5g/kg of soybean oil (25FO), (4) control diet supplemented with 5g/kg of fish oil blend+35g/kg of soybean oil (50FO), and (5) control diet supplemented with 7.5g/kg of fish oil blend+32.5g/kg of soybean oil (75FO). Diets were mixed once daily and fed ad libitum. At the end of the 84-day feeding trial, all animals were slaughtered for carcass characteristics evaluations and meat fat acid profile determination. Animals fed soybean oil had reduced DMI compared to control; however, the average daily gain (ADG), feed efficiency (FE) and final BW were not affected. The animals fed fish oil had similar DMI, ADG, FE and final BW to those receiving the control treatment. The DMI, ADG, FE and final BW were not affected by the increasing substitution of soybean oil for fish oil. Most carcass characteristics were not affected by treatments. The shrink after chilling was lower for the 50FO diet. Short, medium, and long-chain fatty acids were similar for all diets. Stearic acid concentration was higher for lambs fed the fat diets vs. control. However, stearic acid concentration decreased linearly when fish oil replaced soybean oil. Vaccenic acid concentration was higher for lambs fed fat diets vs. control. In addition, vaccenic acid increased linearly with fish oil inclusion. The conjugated linoleic acid (CLA) C18:2 cis-9, trans-11 showed higher concentration in meat of animals fed diets containing fish oil compared to control, but it was not affected by soybean oil inclusion. Feeding small amounts of fish oil blend plus soybean oil does not exert an additional effect on the concentration of CLA C18:2 cis-9, trans-11 in relation to the exclusive use of soybean oil. However, the mixture of 7.5g/kg DM of fish oil blend with 32.5g/kg DM of soybean oil is recommended, because it improves the lipid profile of the meat by increasing the concentration of vaccenic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Additionally, supplementing 7.5g/kg DM of fish oil blend mixed with 32.5g/kg DM of soybean had no negative effect on the feed intake, ADG, FE and carcass characteristics of the lambs fed high concentrate diet.
•Structural behaviour and safety assessment in coaches during frontal collisions.•Contribution to pioneering standard for failure modes and crash behaviour analysis.•Coach vehicle crashworthiness ...study adapting ECE R29 standard.•The current coach body chassis lacks the ability to absorb all the released energy.•The driver and passengers’ physical integrity are compromised.
Accidents involving coaches may endanger the physical integrity of their occupants, since the driver stands very close to the collision region. In the event of a frontal impact, there is a violation of the driver's residual operational space, which depends on the energy of the crash, and this may jeopardize the driver's safety. The most decisive factors in achieving a successful design of structural vehicles is to design innovative solutions that safely control the high energy released as a consequence of the high accelerations involved during impacts. Long-course coaches currently lack design techniques and technologies to absorb in a controlled way the kinetic energy released in the collision. Thus, to fulfill this gap in the passive safety of these vehicles, it is necessary to conduct structural optimization research, to improve the passive safety in the eventual event of a frontal collision. The main goal of this research is to develop new solutions for passive safety used in coaches. To this end, a feasibility study involving experimental and numerical techniques was conducted to assess the improvement of driver safety in case of a frontal impact. This study addresses the need for improved experimental validation and fills a literature gap by developing a realistic testing system and incorporating advanced monitoring techniques for evaluating frontal collisions in vehicles, so a M3 Class III coach was used to conduct this study. Experimentally, the vehicle was subjected to a frontal crash test, whereby the ECE Regulation R29 was considered as the baseline, despite focusing on the certification of heavy vehicles with separate driver's cab. Since no standards are available focusing on coaches, the ECE R29 was used and adapted to the studied model. The experimental testing setup comprises a 2500kg pendulum supported by two steel bars was used. When released it collides with the structure, anchored to the ground, with an energy of 55kJ. Monitoring techniques were employed to track the structure, namely Digital Image Correlation (DIC), strain gauges, and accelerometers. These were placed at specific points to accurately assess the damage evolution of the structure. The experimental results were used to validate the numerical results, obtained using VPS/PamCrash® by FEM techniques. The frontal crash simulation was performed using the Finite Element Method, with an explicit dynamic analysis. Strain evolution, accelerations, and displacements were obtained and compared with the experimental results. Furthermore, the evolution of the kinetic energy is plotted and compared with the reference value of the standard. Through the different obtained outcomes, a determination could be made whether the current models meet the safety criteria or whether a proposed solution is required to enhance its performance. According to the standard guidelines, the present structure has no potential to meet the essential safety requirements. In the future, new alternatives should be explored, leading to a structure that can efficiently absorb all the energy released in the experiment under controlled conditions.
•Ultrasonic frequency in VHCF tests may increase the temperature and can affect the materials’ fatigue performance.•Extreme Gradient Boosting (XGBoost) is an efficient technique to model VHCF ...data.•XGBoost is a non-parametric model usually recommended for datasets with less than 100 thousand observations.•Tree-based machine learning models can be successfully employed to predict the temperature in VHCF tests.
The temperature behavior in very high cycle fatigue (VHCF) testing as well as the influence of the intermittent loading is not completely understood. In many cases the high frequency causes the specimens to heat up and may interfere in the material's fatigue performance. In order to address this issue, this study proposed an experimental test with different stress levels and intermittent driving (pulse-pause) with the aid of non-destructive testing (NDT) using a thermography camera. Specimens were coated with black spray to improve the emissivity to 0.93 and conducted to fully reversed condition (R = −1) up to 107 cycles. A large amount of raw data of pulse, pause, stress amplitude, number of cycles and temperature were recorded. These raw data were used to develop tree-based machine learning models called extreme gradient boosting (XGBoost), capable of predicting the temperature throughout the VHCF tests. The result presented a high performance model with determination coefficients (R2) above 0.98, proving the model to be an important ally for ultrasonic fatigue tests. Additionally, Shapley additive explanation (SHAP) method was adopted to assist in the interpretation of the model results.
Abstract The animal feed science is in constant search for new products that bring economic return, without harming the quality of the final product. This study aimed to evaluate the effect of ...increasing levels of substitution of corn by biscuit bran in lamb diet upon the fatty acid profile of its meat and its physicochemical and sensory characteristics. Twenty-four male lambs divided in four treatments were used. The treatments consisted in increasing levels (0, 15, 30, and 45%) of substitution of corn by biscuit bran in lamb diet. The significance of the treatments was determined by ANOVA and the adjusted means were compared by Tukey test at 5%. The effects were determined by linear and quadratic responses. The use of up to 45% biscuit bran sweet type did not modify the physical and sensory characteristics of meat, just as it did not affect nutrient and dry matter intakes and animal performance. A replacement of 45%, reduces the cholesterol (P = 0.03) and the total content of saturated fatty acid (P = 0.002), not modifying other physicochemical characteristics. The replacement of corn by biscuit bran sweet type in the feeding represents an alternative nutritional strategy for sheep meat production with desirable organoleptic and quality characteristics.
Boronic acid‐derived salicylidenehydrazone complex (BASHY) dyes with a polymethine backbone were designed to yield efficient red‐emitting and two‐photon absorbing fluorophores that can be used as ...markers for astrocytes. The dyes are chemically stable in aqueous solution and do not undergo photodecomposition. Their photophysical properties can be electronically fine‐tuned and thereby adapted to potentially different imaging situations and requirements.
The best of both worlds: BASHY (boronic acid‐derived salicylidenehydrazone complexes) dyes were structurally and electronically integrated with a polymethine backbone, yielding novel fluorophores with highly interesting photophysical properties. The dyes show polarity‐sensitive emission in the red spectral range, significant two‐photon absorption, and improved (photo)chemical stability. They can be designed for bioimaging.
The 2-pentadecyl-2-oxazoline (PEA-OXA) is a natural compound with protective action in neuro-inflammation. We have previously shown that PEA-OXA behaves as an α2 adrenergic receptor (α2AR) antagonist ...and a putative protean agonist on histamine H3 receptors. Recently, neuroinflammation and monoaminergic neurotransmission dysfunction has drawn particular attention in Alzheimer Disease (AD) pathophysiology. In this context, the objective of this study was to investigate the effects of the dual-acting PEA-OXA in an AD-like model in mice. A combined computational and experimental approach was used to evaluate the ability of PEA-OXA to bind α2A-AR subtype, and to investigate the effects of PEA-OXA treatment on neuropathological (behavioural and functional) effects induced by soluble Amyloid β 1–42 (sAβ1–42) intracerebroventricular injection. Computational analysis revealed the PEA-OXA ability to bind the α2A-AR, a pharmacological target for AD, in two alternative poses, one overlapping the Na+ binding site. In vivo studies indicated that chronic treatment with PEA-OXA (10 mg/kg, os) restored the cognitive (discriminative and spatial memory) deficits and social impairments induced by sAβ injection. Consistently, electrophysiological analysis showed a recovery of the long-term potentiation in the hippocampus (Lateral Entorhinal Cortex-Dentate Gyrus pathway), while neuroinflammation, i.e., increased pro-inflammatory cytokines levels and microglia cells density were reduced. These data provide the basis for further investigation of the pro-cognitive aptitude of PEA-OXA by proposing it as an adjuvant in the treatment in AD, for which the available pharmacological approaches remain unsatisfactory. Moreover, this study offers new future direction in research investigating the role of α2AR in neuropsychiatric illness and therapies.
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•PEA-OXA reduces cognitive deficits mediated by Amyloid-β(1−42) intracerebroventricular injection.•PEA-OXA prevents impaired hippocampal synaptic plasticity and neuroinflammation associated with Amyloid-β(1−42).•PEA-OXA may act as a negative allosteric modulator of α2A adrenergic receptor.
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