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In the current economic and energy situation, it is imperative for major electricity consumers to meticulously determine their electricity procurement. This is the case for cement producers. This work intends to determine the most efficient approach to electricity acquisition, considering their involvement in the electricity pool, power-purchase agreements, and the potential installation of a photovoltaic self-production unit and a battery storage system. To achieve this, we model the electricity consumption flexibility of cement producers, accounting for all production processes associated with cement and clinker manufacturing. This results in the formulation of a mid-term decision-making problem under uncertainty, which is addressed through the application of a two-stage risk-averse stochastic programming formulation. In order to reduce the computational size of the resulting optimization problem, the planning horizon is characterized by a set of representative periods obtained through a procedure based on chronological time-period clustering. To analyze the practical viability of the proposed approach, a realistic case study is solved featuring an existing cement producer, real-world energy pool prices, and data pertaining to renewable energy production. The findings derived from this case study highlight the viability of installing a photovoltaic self-production unit as a strategic measure to reduce the expected procurement expenses for the cement producer. Moreover, the photovoltaic self-production unit proves instrumental in mitigating the vulnerability to elevated procurement costs. It has been also observed that an imprecise modeling of the technical characteristics within the cement manufacturing processes can lead to a substantial underestimation of procurement costs.

In urban logistics, effective maintenance is crucial for maintaining the reliability and efficiency of energy supply systems, impacting both asset performance and operational stability. This paper addresses the scheduling and routing plans for maintenance of power generation assets over a multi-period horizon. We model this problem as a multi-period team orienteering problem. To address this multi-period challenge, we propose a dual approach: a novel reinforcement learning (RL) framework and a biased-randomized heuristic algorithm. The RL-based method dynamically learns from real-time operational data and evolving asset conditions, adapting to changes in asset health and failure probabilities to optimize decision making. In addition, we develop and apply a biased-randomized heuristic algorithm designed to provide effective solutions within practical computational limits. Our approach is validated through a series of computational experiments comparing the RL model and the heuristic algorithm. The results demonstrate that, when properly trained, the RL-based model is able to offer equivalent or even superior performance compared to the heuristic algorithm.

Background The optimal strategy for transferring patients to specialized acute stroke care remains controversial. This substudy of the Effect of Direct Transportation to Thrombectomy‐Capable Center vs Local Stroke Center on Neurological Outcomes in Patients with suspected Large‐Vessel Occlusion Stroke in Nonurban Areas (RACECAT) trial aims to investigate the impact of local hospital characteristics and performance on the optimal transport strategy and stroke outcomes. Methods This was a secondary post hoc analysis of the RACECAT trial, evaluating factors potentially associated with functional outcomes among patients initially evaluated at a local stroke center (Local‐SC) versus a thrombectomy‐capable center. The primary outcome was the shift in the 90‐day modified Rankin Scale score in the target population of the RACECAT trial. Door‐to‐needle time, level of care of the Local‐SC (telestroke versus primary stroke center), the specialty of the physician involved with therapeutic decisions, and Local‐SC case volume were assessed for subgroup analyses. Results Of the 1367 patients included in the analysis, 903 had acute ischemic strokes (modified intention to treat). The 90‐day modified Rankin Scale score was associated with door‐to‐needle time in the entire modified intention‐to‐treat cohort (P = 0.026) and in patients initially evaluated in a Local‐SC (P = 0.063), and with local hospital level of care (telestroke versus primary stroke center; P = 0.10). There was a trend favoring direct transport to thrombectomy‐capable center for patients whose assigned Local‐SC was a telestroke center (adjusted odds ratio [OR], 1.47 [95% CI, 0.93–2.33] versus 0.94 [95% CI, 0.71–1.24]; Pinteraction = 0.08) or had door‐to‐needle time over the global median (adjusted OR, 1.52 [95% CI, 0.97–2.40] versus 0.94 [95% CI, 0.71–1.25]; Pinteraction = 0.06). In patients with confirmed large‐vessel occlusion, the benefit of direct transport to thrombectomy‐capable centers when the Local‐SC was a telestroke center (Pinteraction = 0.04) or had longer door‐to‐needle time (Pinteraction = 0.07) was more evident. Conclusions Direct transport to thrombectomy‐capable centers may be preferable in areas primarily covered by telestroke or Local‐SCs with poorer performance, especially in patients with large‐vessel occlusion. These findings can contribute to refining prehospital triage strategies and optimizing stroke systems of care.

The shear strength of asphalt mixtures significantly influences the rut resistance of flexible pavements. Existing methods predominantly address macroscopic aspects, failing to unveil the underlying mechanisms. Moreover, experimental determination of shear strength parameters is time-consuming, but there is a lack of simple prediction methods. This study explores correlations between macroscopic parameters (friction angle and cohesion) and key mesoscopic shear-related factors in Porous Asphalt Mixtures (PAMs) using multiscale triaxial compressive tests, dynamic shear rheometer tests, and sessile drop tests. The research reveals that PAM is influenced not only by aggregate interlock but also by stiff mastic, resulting in a reduced friction angle at a lower temperature. Regression analyses establish a prediction formula for PAMs, incorporating the friction angle of the aggregate skeleton and the complex modulus of the mastic. A correlation function, inspired by Griffith's fracture theory, was also proposed to link PAM's cohesion with the complex modulus and the work of cohesion of mastic, and the friction angle of PAMs. Predictions for PAM's friction angle and cohesion align well with macro-level experimental results, with all the coefficients of determination of over 0.94. These findings enhance the understanding of asphalt mixture shear strength formation and enable shear-resistance optimisation from meso-level.

Introduction In stroke patients, accurate infarct volume assessment at 24 hours typically requires manual segmentation of lesions that often are not well defined. We aimed to validate an automated machine learning algorithm (MethinksFIV) specifically trained to automatically segment and measure subacute infarcts on non‐contrast CT (NCCT) scans. Methods We retrospectively studied stroke patients with a large vessel occlusion prospectively admitted to a comprehensive stroke center. The final infarct volume was segmented on the 24h NCCT manually (man‐FIV) and with the automated method (auto‐FIV). Both measurements were correlated with clinical outcomes. Results We included 346 patients. On 24h‐NCCT median auto‐FIV was lower than man‐FIV (8.6 ml [2.3‐40.7] vs. 16.9 ml [1.1‐70.8], p2 at three months (OR: 1.02 95%CI 1.01‐1.13, p=0.002) than manual segmentation (OR=1.01, 95%CI 1.00‐1.01, p=0.01). In a multivariable analysis, only auto‐FIV remained a significant predictor of mRS>2 at three months (aOR: 1.03 95% CI 1.01‐1.05, p=0.004). Conclusion An automated method to measure subacute infarct volumes in stroke patients is accurate and correlates well with further clinical outcomes. The method appears to outperform manual segmentation and may be used to facilitate infarct characterization in large clinical trials.

Background Our goal is to evaluate whether the administration of thrombolytic treatment has varying effects on clinical and radiological outcomes in patients with large‐vessel occlusion stroke, based on the type of stroke center where the treatment was given (thrombectomy‐capable center versus local stroke center). Methods We included patients with an acute ischemic large‐vessel occlusion stroke who were directly admitted to thrombectomy‐capable centers and treated with endovascular thrombectomy, or were transferred from local stroke centers as thrombectomy candidates, in Catalonia, Spain, between 2017 and 2021. The primary outcome was the shift analysis on the modified Rankin scale score at 90 days. Secondary outcomes included death at 90 days and the rate of parenchymal hemorrhage and successful reperfusion. Inverse‐probability weighting clustered at the type of stroke center was used to estimate the effects. Results The analysis included 2268 patients directly admitted to thrombectomy‐capable centers, of whom 975 (49%) were treated with thrombolysis, and 938 patients transferred from local stroke centers, of whom 580 (66%) were treated with thrombolysis and 616 (67%) were treated with thrombectomy. Mean age was 72 (SD ±13) years, median National Institute of Health Stroke Scale score was 17 (interquartile range, 12–21), and 1363 patients were women (48%). Patients treated with intravenous thrombolysis were younger, had shorter time from onset to first image, higher Alberta Stroke Program Early Computed Tomography Score, and lower rates of wake‐up stroke, atrial fibrillation, and anticoagulation intake. Patients treated with thrombolysis had better functional outcome at 90 days, with no difference between patients directly admitted to thrombectomy‐capable centers (adjusted common odds ratio [acOR], 1.50 [95% CI, 1.24–1.81]) and patients transferred from local stroke centers (acOR, 1.44 [95% CI, 1.04–2.01]). Patients treated with intravenous thrombolysis had lower death rate, higher rate of parenchymal hematoma, and similar rate of successful reperfusion, with no difference according to type of center (Pinteraction>0.1). Conclusion Administration of intravenous thrombolysis in patients with a large‐vessel stroke with intention of thrombectomy was associated with lower degrees of disability, lower death rate, and higher rates of parenchymal hematoma both in thrombectomy‐capable centers and in local stroke centers.

Audiovisual media are an essential source of information and leisure in our lives, but people with hearing disabilities lose the emotional content that is intended to be transmitted through this channel. Some previous studies have tried to find alternative ways to elicit these emotions using other sensory channels, and some attempts have been made with haptic systems synchronized with rhythms of music and action in movies, but they fail in studying deeply the provoked neural response. In this article, we propose the tactile channel as the alternative to the auditory channel to convey the emotions generated by audiovisual events, measuring the effect of a proprietary system in the emotions by monitoring neural response. We have developed a low-cost system consisting of an Arduino Uno, a pair of gloves with micromotors and a driver. Using EEG, we have measured brain activity generated during audiovisual stimulation of a short film with clearly negative emotional content, with and without synchronized tactile stimuli, in two groups of people, one without hearing impairment and the other with hearing impairment. We have used the Hotelling’s T2 test as a multivariate statistical analysis of EEG measurements. Comparing the difference in brain activation generated in the conditions with and without vibration in both groups, we have found that multimodal stimulation by touch and associated with audiovisual stimuli enhances in a 30% the emotional, attentional, and auditory circuits activation, due to brain reorganization around frontal and parietal structures (all related to emotional responses) in the hearing-impaired group.

Asphalt concrete is widely known to be a self-healing material, by repeated loading the micro-cracks have appearing and disappeared when both faces of a fissure touch. This process is applied until the crack is completely gone and the material regains its prior resistance. In this study, two strategies are presented to boost of healing rate and applied in porous asphalt, one of them is induction heating. This method is used by mixing 1.1% of steel wool fiber to speed up this phenome, with 20mm aggregate size for porous asphalt mixture and 21% air voids content. Another approach is self-healing by 0.5% encapsulated agents using. These capsulate are incorporated within the asphalt mixture, then the capsules break when subjected to repeating loading on the asphalt surface. It has been discovered that there is a moment in the lifespan of an asphalt road where the capsules or induction heating applied can successfully self-heal the existing crack damage.

This paper investigates the strength development of fly ash (FA)-based geopolymer paste cured by thermal and microwave radiations, together with microstructural characterisations. The results indicate that both the two methods can significantly increase the compressive strength compared to room temperature curing. Higher microwave power can promote the strength development without changing the reaction products and the final strength, owing to the accelerated formation of N-A-S-H in the reaction product under the raised temperature, characterised by the increased Si–O Q2-3 bonds and decreased Si/Al ratio. Over-time microwave radiation weakens the strength due to the formation of micro-cracks. Microwave presents higher curing efficiency than heating, producing a compressive strength of 37 MPa within 15 min. Moreover, microwave radiation can accelerate the setting progress of the fresh paste without compromising its final strength after curing. The present work can guide the preparation of FA-based geopolymers with high early strength in practice.

Introduction Simultaneous tPA administration during mechanical thrombectomy may induce synergistic benefits (1). We aimed to characterize the hypoperfusion status after thrombectomy according to the timing of tPA administration and the degree of final recanalization. Methods We studied consecutive anterior circulation large vessel occlusion (LVO) stroke patients treated with mechanical thrombectomy who received a CT perfusion (CTP) immediately after endovascular procedure (2). Patients were divided in three groups according to: no iv tPA treatment (non‐tPA), tPA administration before 120 minutes (tPA>120) or iv tPA administration within 120 min (tPA< 120) of groin puncture. The extend of post‐procedure hypoperfusion (volume Tmax>6s) and relative hypoperfusion reduction compared with admission CTP (volume post‐procedure – admission Tmax>6s/admission Tmax>6s) according to final TICI scores were compared between the three study groups. Results One hundred and sixty‐nine patients were included in the study, mean age 72 years and median baseline NIHSS of 15. Thirty (17.8%) patients received iv tPA more than 2h before groin puncture (tPA>120), 32(18.9%) within 2h of the puncture (tPA < 120) and 107(63.3%) were non‐tPA. No difference on stroke severity, pre‐procedure hypoperfusion volume or occlusion location before thrombectomy were detected between groups. The rate of complete recanalization (TICI 3, 38.5%) was also similar in the 3 study groups (p = 0.12). Overall, the post‐procedure hypoperfusion volume was significantly lower in the tPA< 120 group (19.9±4.6cc vs 35.0±5.5, p = 0.04), and the relative hypoperfusion reduction was higher in tPA< 120 (0.86 vs 0.66, p = 0.05) as compared to non‐tPA. No significant differences were detected between non‐tPA and tPA>120 groups. For each final TICI score the post‐procedure hypoperfusion tended to be lower in the tPA< 120‐group, with a stronger reduction in patients with lower degree of recanalization (Figure). Conclusions A reduction of post‐thrombectomy hypoperfusion volumes was detected in patients treated with iv tPA during or shortly before thrombectomy, which could be a surrogate marker of the beneficial effect of tPA on the microcirculation. The specific reperfusion synergistic effect of tPA and mechanical thrombectomy beyond LVO recanalization warrants future studies.

Background: In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding 2 wk (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin, and procalcitonin) but were less likely to present with clinical symptoms (p≤0.01). By country-adjusted multivariable logistic regression analyses, cancer was not found to be an independent risk factor for 30 day mortality (p=0.18), whereas lymphopenia was independently associated with increased mortality in all patients and in patients with cancer. Older age (≥65y) was the strongest predictor of 30 day mortality in all patients (OR = 4.47, p

Background: Characterization of atrial myocardial infarction is hampered by the frequent concurrence of ventricular infarction. Theoretically, atrial infarct scarring could be recognized by multifrequency tissue impedance, like in ventricular infarction, but this remains to be proven.Objective: This study aimed at developing a model of atrial infarction to assess the potential of multifrequency impedance to recognize areas of atrial infarct scar. Methods: Seven anesthetized pigs were submitted to transcatheter occlusion of atrial coronary branches arising from the left coronary circumflex artery. Six weeks later the animals were anesthetized and underwent atrial voltage mapping and multifrequency impedance recordings. The hearts were thereafter extracted for anatomopathological study. Two additional pigs not submitted to atrial branch occlusion were used as controls.Results: Selective occlusion of the atrial branches induced areas of healed infarction in the left atrium in 6 of the 7 cases. Endocardial mapping of the left atrium showed reduced multi-frequency impedance (Phase angle at 307 kHz: from −17.1° ± 5.0° to −8.9° ± 2.6°, p < .01) and low-voltage of bipolar electrograms (.2 ± 0.1 mV vs. 1.9 ± 1.5 mV vs., p < .01) in areas affected by the infarction. Data variability of the impedance phase angle was lower than that of bipolar voltage (coefficient of variability of phase angle at307 kHz vs. bipolar voltage: .30 vs. .77). Histological analysis excluded the presence of ventricular infarction.Conclusion: Selective occlusion of atrial coronary branches permits to set up a model of selective atrial infarction. Atrial multifrequency impedance mapping allowed recognition of atrial infarct scarring with lesser data variability than local bipolar voltage mapping. Our model may have potential applicability on the study of atrial arrhythmia mechanisms.

Objectives To evaluate effectiveness and safety of certolizumab pegol (CZP) in uveitis due to immune-mediated inflammatory diseases (IMID).Methods Multicentre study of CZP-treated patients with IMID uveitis refractory to conventional immunosuppressant. Effectiveness was assessed through the following ocular parameters: best-corrected visual acuity, anterior chamber cells, vitritis, macular thickness and retinal vasculitis. These variables were compared between the baseline, and first week, first, third, sixth months, first and second year.Results We studied 80 (33 men/47 women) patients (111 affected eyes) with a mean age of 41.6±11.7 years. The IMID included were: spondyloarthritis (n=43), Behçet’s disease (n=10), psoriatic arthritis (n=8), Crohn’s disease (n=4), sarcoidosis (n=2), juvenile idiopathic arthritis (n=1), reactive arthritis (n=1), rheumatoid arthritis (n=1), relapsing polychondritis (n=1),Conclusions CZP seems to be effective and safe in uveitis related to different IMID, even in patients refractory to previous biological drugs.

Background Door‐in–door‐out time (DIDO) in nonthrombectomy stroke centers is a key performance indicator in acute stroke care. Nonetheless, the relative importance of DIDO on outcome in patients transferred for endovascular treatment (EVT) is not widely known. Therefore, we aim to explore the association between DIDO and clinical outcome according to onset to reperfusion time in patients undergoing EVT. Methods Observational multicenter study including patients transferred to a thrombectomy‐capable center from a local stroke center who underwent thrombectomy. The primary outcome was favorable clinical outcome, as evaluated by a modified Rankin Scale score of 0 to 2 at 3 months. We evaluated the association between DIDO and clinical outcome according to onset to reperfusion time and factors related to shorter DIDO time. Results Among 2710 patients transferred for thrombectomy evaluation, 970 (43.8%) patients received EVT. Median baseline National Institutes of Health Stroke Scale and DIDO time were 12 (interquartile range [IQR], 6–19) and 83 minutes (IQR, 66–108), respectively. Among patients undergoing EVT, no association was found between DIDO and clinical outcome. Considering only patients treated in the early time window (onset to reperfusion time ≤240 minutes), patients with favorable outcome had a shorter DIDO (60 [IQR, 52–68] versus 73 [IQR, 61–83] minutes; P=0.013). A receiver operating characteristic curve identified a cutoff of 67 minutes of DIDO time that better predicted favorable outcome (sensitivity, 70%; specificity, 73%; area under the curve, 0.741). A multivariate analysis showed that DIDO ≤67 minutes emerged as an independent factor associated with favorable outcome (odds ratio [OR], 5.29 [95% CI, 1.38–20.27]; P=0.015). Door to computed tomography time was the only factor associated with DIDO ≤67 minutes (OR, 1.113 [95% CI, 1.018–1.261]; P=0.022) in a multivariate analysis in this time frame. Conclusions In transferred patients undergoing EVT, DIDO has a significant impact on clinical outcome, mainly in the first hours from stroke onset. A benchmark of 67 minutes in DIDO time is proposed. Shorter door to computed tomography time appears to be an independent factor associated to achieve DIDO time ≤67 minutes. Measures to optimize workflow into referral centers are warranted.

Culture environment during in vitro embryo production can affect embryo phenotype and pregnancy outcomes, making culture modifications a logical approach for improving embryo competence. Previously, the addition of the growth factors FGF2, LIF, and IGF1, termed FLI, to the culture medium improved bovine embryo development, and re-expansion following cryopreservation. The objective of this study was to investigate the survival of cryopreserved FLI treated embryos at day 15 of pregnancy and evaluate conceptus transcriptomes. Embryos were produced using in vitro fertilization of abattoir-derived oocytes, cultured to the blastocyst stage in the presence or absence of FLI (+/- FLI), and cryopreserved by slow-rate freezing. Thawed embryos were transferred into non-lactating recipient beef cows and eight days later conceptuses were recovered and analyzed. For a subset of conceptuses whole transcriptome analysis was performed by using the NovaSeq 6000. There was no detectable difference in conceptus recovery or average conceptus length between the two groups. There were 32 differentially expressed transcripts, 23 up-regulated and nine down-regulated in the +FLI group compared to -FLI. Genes were involved in interferon signaling, prostaglandin synthesis, and placental development. This study reveals that embryos cultured with or without FLI and cryopreserved by slow-rate freezing have similar developmental competence up to day 15 of development. Nevertheless, differences in gene expression exhibit an effect of FLI on conceptus signaling during elongation.

Summary: Disturbances in lipid metabolism in the CNS contribute to neurodegeneration and cognitive impairments. Through tight metabolic coupling, astrocytes provide energy to neurons by delivering lactate and cholesterol and by taking up and processing neuron-derived peroxidated fatty acids (pFA). Disruption of CNS lipid homeostasis is observed in people who use cocaine and in several neurodegenerative disorders, including HIV. The brain’s main source of energy is aerobic glycolysis, but numerous studies report a switch to β-oxidation of FAs in response to cocaine. Unlike astrocytes, in response to cocaine, neurons cannot efficiently consume excess pFAs for energy. Accumulation of pFA in neurons induces autophagy and release of pFA. Astrocytes endocytose the pFA for oxidation as an energy source. Our data show that blocking mitochondrial/cytosolic citrate transport reduces the neurotrophic capacity of astrocytes, leading to decreased neuronal fitness.

Summary: Background: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p

Since it is observed that the consumption of herbal dietary supplements is increasing, we aimed to research whether front-of-pack risk and benefit information influences a consumer’s intention to use (ITU) a dietary supplement.A total of 268 subjects participated in an online questionnaire, in which they were exposed to one of four different labels with risk and/or benefit information about the product, and were provided with additional risk-benefit information. Their ITU was measured at three time points: after exposure to the label, after reading the additional information and after a wash-out period.The results from our study showed that information on the label did not significantly impact the ITU. In all groups, ITU significantly increased after exposure to detailed information, and again after the wash-out period.We therefore conclude that front-of-pack information did not influence a consumer’s intention to use dietary supplements, but additional information may have influenced their intentions.

The seven mammalian FXYD proteins associate closely with α/β heterodimers of Na+/K+-ATPase. Most of them protect the β1 subunit against glutathionylation, an oxidative modification that destabilizes the heterodimer and inhibits Na+/K+-ATPase activity. A specific cysteine (Cys) residue of FXYD proteins is critical for such protection. One of the FXYD proteins, FXYD3, confers treatment resistance when overexpressed in cancer cells. We developed two FXYD3 peptide derivatives. FXYD3-pep CKCK retained the Cys residue that can undergo glutathionylation and that is critical for protecting the β1 subunit against glutathionylation. FXYD3-pep SKSK had all Cys residues mutated to Serine (Ser). The chemotherapeutic doxorubicin induces oxidative stress, and suppression of FXYD3 with siRNA in pancreatic- and breast cancer cells that strongly express FXYD3 increased doxorubicin-induced cytotoxicity. Exposing cells to FXYD3-pep SKSK decreased co-immunoprecipitation of FXYD3 with the α1 Na+/K+-ATPase subunit. FXYD3-pep SKSK reproduced the increase in doxorubicin-induced cytotoxicity seen after FXYD3 siRNA transfection in pancreatic- and breast cancer cells that overexpressed FXYD3, while FXYD3-pep CKCK boosted the native protein’s protection against doxorubicin. Neither peptide affected doxorubicin’s cytotoxicity on cells with no or low FXYD3 expression. Fluorescently labeled FXYD3-pep SKSK was detected in a perinuclear distribution in the cells overexpressing FXYD3, and plasmalemmal Na+/K+-ATPase turnover could not be implicated in the increased sensitivity to doxorubicin that FXYD3-pep SKSK caused. FXYD peptide derivatives allow rapid elimination or amplification of native FXYD protein function. Here, their effects implicate the Cys residue that is critical for countering β1 subunit glutathionylation in the augmentation of cytotoxicity with siRNA-induced downregulation of FXYD3.

Abstract Aims The prognostic value of biomarkers in patients with heart failure (HF) and mid‐range (HFmrEF) or preserved ejection fraction (HFpEF) has not been widely addressed. The aim of this study was to assess whether the prognostic value of growth differentiation factor 15 (GDF‐15) is superior to that of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) in patients with HFmrEF or HFpEF. Methods and results Heart failure patients with either HFpEF or HFmrEF were included in the study. During their first visit to the HF unit, serum samples were obtained and stored for later assessment of GDF‐15 and NT‐proBNP concentrations. Patients were followed up by the HF unit. The main endpoint was all‐cause mortality. A total of 311 patients, 90 (29%) HFmrEF and 221 (71%) HFpEF, were included. Mean age was 72 ± 13 years, and 136 (44%) were women. No differences were found in GDF‐15 or NT‐proBNP concentrations between both HF groups. During a median follow‐up of 15 months (Q1–Q3: 9–30 months), 98 patients (32%) died, most (71%) of cardiovascular causes. Patients who died had higher median concentrations of GDF‐15 (4085 vs. 2270 ng/L, P < 0.0001) and NT‐proBNP (1984 vs. 1095 ng/L, P < 0.0001). A Cox multivariable model identified New York Heart Association Functional Class III (P = 0.04), systolic blood pressure (P = 0.01), left atrial diameter (P = 0.03), age >65 years (P < 0.0001), and GDF‐15 concentrations (P = 0.01) but not NT‐proBNP as independent predictors of all‐cause mortality. The area under the curve was 0.797 for the basic model including NT‐proBNP, and the area under the curve comparing the overall model was 0.819, P = 0.016 (DeLong's test). Integrated discrimination improvement index after the inclusion of GDF‐15 in the model with the mortality risk factors was 0.033; that is, the ability to predict death increased by 3.3% (P = 0.004). Net reclassification improvement was 0.548 (P < 0.001); that is, the capacity to improve the classification of the event (mortality) was 54.8%. GDF‐15 concentrations were divided in tertiles (4330 ng/L), and survival curves were evaluated using the Kaplan–Meier technique. Patients in the highest tertile had the poorest 5 year survival, at 16%, whereas the lowest tertile had the best survival, of 78% (P < 0.001). Conclusions Growth differentiation factor 15 was superior to NT‐proBNP for assessing prognosis in patients with HFpEF and HFmrEF. GDF‐15 emerges as a strong, independent biomarker for identifying HFmrEF and HFpEF patients with worse prognosis.

Abstract Background Diseases and disorders with a chronic neuroinflammatory component are often linked with changes in brain metabolism. Among neurodegenerative disorders, people living with human immunodeficiency virus (HIV) and Alzheimer’s disease (AD) are particularly vulnerable to metabolic disturbances, but the mechanistic connections of inflammation, neurodegeneration and bioenergetic deficits in the central nervous system (CNS) are poorly defined. The particularly interesting new cysteine histidine-rich-protein (PINCH) is nearly undetectable in healthy mature neurons, but is robustly expressed in tauopathy-associated neurodegenerative diseases including HIV infection and AD. Although robust PINCH expression has been reported in neurons in the brains of patients with HIV and AD, the molecular mechanisms and cellular consequences of increased PINCH expression in CNS disease remain largely unknown. Methods We investigated the regulatory mechanisms responsible for PINCH protein-mediated changes in bioenergetics, mitochondrial subcellular localization and bioenergetic deficits in neurons exposed to physiological levels of TNFα or the HIV protein Tat. Changes in the PINCH-ILK-Parvin (PIP) complex association with cofilin and TESK1 were assessed to identify factors responsible for actin depolymerization and mitochondrial mislocalization. Lentiviral and pharmacological inhibition experiments were conducted to confirm PINCH specificity and to reinstate proper protein-protein complex communication. Results We identified MEF2A as the PINCH transcription factor in neuroinflammation and determined the biological consequences of increased PINCH in neurons. TNFα-mediated activation of MEF2A via increased cellular calcium induced PINCH, leading to disruption of the PIP ternary complex, cofilin activation by TESK1 inactivation, and actin depolymerization. The disruption of actin led to perinuclear mislocalization of mitochondria by destabilizing the kinesin-dependent mitochondrial transport machinery, resulting in impaired neuronal metabolism. Blocking TNFα-induced PINCH expression preserved mitochondrial localization and maintained metabolic functioning. Conclusions This study reported for the first time the mechanistic and biological consequences of PINCH expression in CNS neurons in diseases with a chronic neuroinflammation component. Our findings point to the maintenance of PINCH at normal physiological levels as a potential new therapeutic target for neurodegenerative diseases with impaired metabolisms.

Standard captioning for the deaf and hard of hearing people cannot transmit the emotional information that music provides in support of the narrative in audio-visual media. We explore an alternative method using vibrotactile stimulation as a possible channel to transmit the emotional information contained in an audio-visual soundtrack and, thus, elicit a greater emotional reaction in hearing-impaired people. To achieve this objective, we applied two one-minute videos that were based on image sequences that were unassociated with dramatic action, maximizing the effect of the music and vibrotactile stimuli. While viewing the video, using EEG we recorded the brain activity of 9 female participants with normal hearing, and 7 female participants with very severe and profound hearing loss. The results show that the same brain areas are activated in participants with normal hearing watching the video with the soundtrack, and in participants with hearing loss watching the same video with a soft and rhythmic vibrotactile stimulation on the palm and fingertips, although in different hemispheres. These brain areas (auditory cortex, superior temporal cortex, medial frontal cortex, inferior frontal gyrus, superior temporal pole and insula) have been consistently reported as areas involved in the emotional perception of music. We conclude that vibrotactile stimuli can generate cortex activation while watching audio-visual media in a similar way to sound. Thus, a further in-depth study of the possibilities of these stimuli can contribute to an alternative subtitling channel for enriching the audiovisual experience of hearing-impaired people.

Glucose tolerance tests (GTT) are commonly performed in beef cattle to evaluate the glucose-insulin signaling pathway. Blood samples are obtained via a catheter and then transferred back to the laboratory for further analysis. A hand-held glucometer used chute-side can make performing GTT's and quantifying blood glucose concentration much easier and faster for research purposes. The purpose of this study was to evaluate the agreement between a hand-held electronic glucometer (Precision Xtra; Abbott Diabetes Care Inc., Mississauga, ON, Canada) for chute-side use in beef cattle compared with a colorimetric assay in the laboratory (Stanbio Glucose LiquiColor; Stanbio Laboratory, Boerne, TX, USA). A GTT was performed on 13 Simmental × Angus steers during the growing phase. Blood samples were obtained via a jugular catheter. Glucometer readings were taken immediately after blood was sampled from the jugular with no preservative, and laboratory measurements were conducted on plasma preserved with sodium fluoride. A paired t-test (P = 0.40), Pearson's correlation (P < 0.001; r = 0.95), Bland-Altman plot, and Lin's concordance correlation coefficient (LCCC = 0.90) were completed to evaluate the performance of the glucometer relative to the results from the laboratory assay. Based on the results, we conclude that the glucometer is an acceptable method for measuring blood glucose concentration in beef cattle under field conditions.

Background: The use of telemedicine has increased to address the ongoing healthcare needs of patients with movement disorders.Objective: We aimed to describe the technical and basic security features of the most popular telemedicine videoconferencing software.Methods: We conducted a systematic review of articles/websites about “Telemedicine,” “Cybersecurity,” and “Videoconferencing software.” Technical capabilities and basic security features were determined for each videoconferencing software.Results: Twenty-six videoconferencing software programs were reviewed, 13 (50.0%) were specifically designed for general healthcare, and 6/26 (23.0%) were compliant with European and US regulations. Overall technical and security information were found in 5/26 software (19.2%), including Microsoft Teams, Google Hangout, Coviu, Doxy.me, and Thera platforms.Conclusions: Detailed information about technical capabilities and data security of videoconferencing tools is not easily and openly retrievable. Our data serves as a guide for practitioners seeking to understand what features should be examined when choosing software and what options are available.

Objective To evaluate peripheral nerve involvement in patients with SLE with neuromuscular ultrasonography (NMUS) and understand its role in investigating SLE-related peripheral neuropathy.Methods This is an observational cross-sectional study on patients with SLE and healthy controls. Five nerves in each patient were examined bilaterally with NMUS, and the cross-sectional area (CSA) of each nerve at certain sites was estimated. The mean CSA at each site, for each nerve, in each group was statistically analysed and compared between groups.Results 370 nerves were evaluated in 37 patients. By nerve conduction study (NCS), 36 patients had polyneuropathy (80.6% mixed type, 19.4% sensory). Significant mean CSA enlargement was present among the ulnar nerve at the Guyon’s canal and mid-humerus (both p=0.001); tibial nerve at the distal leg and proximal to the tarsal tunnel (p=0.003 and p=0.001, respectively); and peroneal nerve at the popliteal fossa (p=0.042). The mean CSA showed high specificity compared with NCS.Conclusion Our study shows that CSA could be a complementary tool to NCS for studying peripheral neuropathy in SLE. Furthermore, NMUS provides data on the different pathophysiological aspects of nerve involvement in SLE. Future studies using more than one sonographic parameter in combination with NCS and nerve histopathology are recommended to further investigate SLE-related neuropathy.Trial registration number NCT04527172.

This paper aims to assess the influence of encapsulated rejuvenators on plant-produced asphalt’s performance. The polymeric capsules are evaluated as cellular materials that deform and absorb energy while they experience a progressive collapse of their porous structure, rather than a simply means to release the rejuvenator. Additionally, variables during asphalt manufacturing that may affect their plastic deformation under loading are assessed too. Firstly, plant-produced asphalt’s mechanical and morphological properties were evaluated, including the capsules’ distribution and integrity after mixing. Then, results were contrasted with lab-produced asphalt under controlled conditions. Lastly, the capsules’ deformation was qualitatively evaluated using a FE model to verify findings from the testing campaign. It was concluded that (i) cellular capsules can resist mixing at an asphalt plant without compromising their performance; (ii) the deformation of the capsules affected asphalt’s stability by up to 13%, reduced the particle loss by up to 25% and increased asphalt’s macrotexture by 10%; (iii) to maximize their energy absorption, the cellular capsules must be part of the aggregate skeleton.

BackgroundApproximately 40-70% of people with Parkinson's disease (PD) fall each year, causing decreased activity levels and quality of life. Current fall-prevention strategies include the use of pharmacological and non-pharmacological therapies. To increase the accessibility of this vulnerable population, we developed a multidisciplinary telemedicine program using an Information and Communication Technology (ICT) platform. We hypothesized that the risk for falling in PD would decrease among participants receiving a multidisciplinary telemedicine intervention program added to standard office-based neurological care.ObjectiveTo determine the feasibility and cost-effectiveness of a multidisciplinary telemedicine intervention to decrease the incidence of falls in patients with PD.MethodsOngoing, longitudinal, randomized, single-blinded, case-control, clinical trial. We will include 76 non-demented patients with idiopathic PD with a high risk of falling and limited access to multidisciplinary care. The intervention group (n = 38) will receive multidisciplinary remote care in addition to standard medical care, and the control group (n = 38) standard medical care only. Nutrition, sarcopenia and frailty status, motor, non-motor symptoms, health-related quality of life, caregiver burden, falls, balance and gait disturbances, direct and non-medical costs will be assessed using validated rating scales.ResultsThis study will provide a cost-effectiveness assessment of multidisciplinary telemedicine intervention for fall reduction in PD, in addition to standard neurological medical care.ConclusionIn this challenging initiative, we will determine whether a multidisciplinary telemedicine intervention program can reduce falls, as an alternative intervention option for PD patients with restricted access to multidisciplinary care.Trial registrationClinicalTrials.gov Identifier: NCT04694443.

Current patterns of preventive antibiotic prescribing are encouraging the spread of antimicrobial resistance. Recently, the Spanish Society of Implants (SEI) developed the first clinical practice guidelines published to date, providing clear guidelines on how to prescribe responsible and informed preventive antibiotic therapy (PAT) based on the available scientific evidence on dental implant treatments (DIs). The present document aims to summarise and disseminate the recommendations established by this expert panel. These were based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were analysed using the Scottish Intercollegiate Guidelines Network (SIGN) checklist templates and ranked according to their level of evidence. They were then assigned a level of recommendation using the Grading of Recommendations, Assessment, Development and Evaluation system (GRADE). Guidelines were established on the type of PAT, antibiotic and dosage of administration in the placement of DIs without anatomical constraints, in bone augmentation with the placement of DIs in one or two stages, placement of immediate DIs, sinus elevations, implant prosthetic phase, as well as recommendations in patients allergic to penicillin. Therefore, the PAT must be adapted to the type of implant procedure to be performed.

Current state-of-the-art techniques for the solid phase synthesis of molecularly imprinted polymer (MIP) nanoparticles typically rely on amino silanes for the immobilisation of template molecules prior to polymerisation. An investigation into commonly used amino silanes identified a number of problematic side reactions which negatively affect the purity and affinity of these polymers. Iodo silanes are presented as a superior alternative in a case study describing the synthesis of MIPs against epitopes of a common cancer biomarker, epidermal growth factor receptor (EGFR). The proposed iodo silane outperformed the amino silane by all metrics tested, showing high purity and specificity, and nanomolar affinity for the target peptide.

The saliva of COVID-19-confirmed patients presents a high viral load of the virus. Aerosols generated during medical and dental procedures can transport the virus and are a possible causative agent of cross-infection. Since the onset of the pandemic, numerous investigations have been attempting to mitigate the risk of transmission by reducing the viral load in saliva using preprocedural mouthwashes. This study aims to review the most up-to-date in vitro and in vivo studies investigating the efficacy of different mouthwashes on reducing the salivary viral load of SARS-CoV-2, giving particular attention to the most recent randomized control trials published.

As the population ages, more and more patients with orthopaedic prostheses (OPs) require dental implant treatment. Surveys of dentists and orthopaedic surgeons show that prophylactic antibiotics (PAs) are routinely prescribed with a very high frequency in patients with OPs who are about to undergo dental procedures. The present study aims to determine the need to prescribe prophylactic antibiotic therapy in patients with OPs treated with dental implants to promote their responsible use and reduce the risk of antimicrobial resistance. An electronic search of the MEDLINE database (via PubMed), Web of Science, LILACS, Google Scholar, and OpenGrey was carried out. The criteria used were those described by the PRISMA® Statement. No study investigated the need to prescribe PAs in patients with OPs, so four studies were included on the risk of infections of OPs after dental treatments with varying degrees of invasiveness. There is no evidence to suggest a relationship between dental implant surgeries and an increased risk of OP infection; therefore, PAs in these patients are not justified. However, the recommended doses of PAs in dental implant procedures in healthy patients are the same as those recommended to avoid infections of OPs.

This paper analyzes a flexible job shop scheduling problem with operators and is motivated by a real-life case study of the aeronautical industry, where each process can be performed on alternative machines (shared by multiple products) and requires not only machines but also some operators to execute the process. One goal of this scheduling is to minimize the number of operators and airframes that are needed in the assembly line. Minimizing the number of airframes in the assembly line, which is particularly important due to the cost of each airframe, is generally ignored in production planning models that are used in prior studies. Moreover, the output of the program refers to a set of schedules that includes different combinations of number of operators and intermediate stock, to enable a better decision making. A mixed integer linear programming model is presented to solve this problem. Experimentation was conducted using real-life examples from the aeronautical industry. The solutions that are presented in this paper outperformed current industrial methods in both quality and calculation time. To the best of our knowledge, this variant has not been addressed in prior studies either in scheduling or in aeronautics contexts. However, minimizing the number of operators and intermediate stock could have significant implications for numerous labor intensive industries, contributing to enhanced and more agile decision making processes.

Abstract Salty taste is one of the five basic tastes and is often elicited by NaCl. Because excess sodium intake is associated with many health problems, it could be useful to have salt taste enhancers that are not sodium based. In this study, the regulation of NaCl-induced responses was investigated in cultured human fungiform taste papillae (HBO) cells with five arginyl dipeptides: Ala-Arg (AR), Arg-Ala (RA), Arg-Pro (RP), Arg-Glu (RE), and Glu-Arg (ER); and two non-arginyl dipeptides: Asp-Asp (DD) and Glu-Asp (ED). AR, RA, and RP significantly increased the number of cell responses to NaCl, whereas no effect was observed with RE, ER, DD, or ED. We also found no effects with alanine, arginine, or a mixture of both amino acids. Pharmacological studies showed that AR significantly increased responses of amiloride-sensitive but not amiloride-insensitive cells. In studies using small interfering RNAs (siRNAs), responses to AR were significantly decreased in cells transfected with siRNAs against epithelial sodium channel ENaCα or ENaCδ compared to untransfected cells. AR dramatically increased NaCl-elicited responses in cells transfected with NHE1 siRNA but not in those transfected with ENaCα or ENaCδ siRNAs. Altogether, AR increased responses of amiloride-sensitive cells required ENaCα and ENaCδ.

Cold mix asphalt, a promising substitute for conventional hot mix asphalt, is manufactured at ambient temperature using bitumen emulsion as binder. To improve its strength and durability, cement is often added to the mixture. This review (1) presents an overview about advances in cold mix asphalt modified with cementitious materials, often called CBEA (cement bitumen emulsion asphalt), (2) illustrates advantages and disadvantages of CBEA and (3) gives recommendations to produce homogenous CBEA mixtures

Using the ac-calorimetry technique and the electric modulus formalism for analysis of ionic conductivity relaxation in crystalline γ-RbAg4I5, close to the γ to β phase transition at 120 K, the temperature derivative of microscopic interaction energy for a single-mobile ion is proportional to the specific heat. The two different experimental techniques show that cooperative behavior drives the phase transition at 120 K (obey the same mechanism). Keywords: Electric modulus formalism, β-correlation function, ac-calorimetry technique

Introduction: Various studies have reported the effect of fluoride on the surface of dental enamel in preventing the development of carious lesions. Research conducted on the effect of fluoride on demineralization and remineralization has reported on the in vitro pH cycling model, in which samples of enamel or dentin were subjected to pH changes, such as those occurring in the oral cavity, to reduce the advancement of the cavitated lesions. Aim: To evaluate the remineralization of dental enamel after the application of three fluorinated compounds commonly used in paediatric dentistry sodium fluoride, acidulated phosphate fluoride, and silver diamine fluoride and the effect on enamel microhardness under pH cycling conditions. Materials and Methods: Sixty impacted 3rd molars, with intact anatomical crowns recently extracted and without repaired structural defects, were sectioned longitudinally in a mesiodistal direction using a diamond disc, obtaining two working surfaces (buccal and lingual). The 120 working surfaces obtained were immersed for 96 hours in a demineralization solution at 37°C in order to demineralize the enamel surface. All of the demineralized molars were then randomly divided into four groups (n=30 each) and their surfaces were treated with Silver diamine fluoride (SDF), Difluoride silane (DSF), and Acidulated phosphate fluoride (APF), and with no treatment undertaken in the Control group (CG). The samples were immersed in alternating solutions for demineralization and remineralization at pH 4.4 and pH 7.0, respectively. The Vickers hardness number (VHN) was determined after 5, 10, and 15 days using a microdurometer with a load of 25 gf for 20s. Data were analysed using the ANOVA statistical test. Results: The microhardness values obtained from the three remineralization groups (SDF, DSF and APF) were obtained, with the mean microhardness after 10 days of treatment higher in the occlusal and cervical areas and statistically significant differences were found (SDF p=0.016, DSF p=0.043 and APF p=0.035). By Day 15, an increase in mean microhardness was found in the SDF and DSF groups at different depths recorded, and statistically significant differences were found. Conclusion: We found a significant difference among the effects of the three fluorinated compounds (SDF, DSF and APF) on the enamel surface. This finding is clinically significant as the use of remineralizing agents such as SDF, DSF and APF increases the microhardness of the enamel surface, suggesting that fluorinated compounds are effective in the reduction and remineralization of incipient carious lesions in dental enamel.

This paper demonstrates the use of peridynamics and discrete multiphysics to assess micro crack formation and propagation in asphalt at low temperatures and under freezing conditions. Three scenarios are investigated: (a) asphalt without air voids under compressive load, (b) asphalt with air voids and (c) voids filled with freezing water. The first two are computed with Peridynamics, the third with peridynamics combined with discrete multiphysics. The results show that the presence of voids changes the way cracks propagate in the material. In asphalt without voids, cracks tend to propagate at the interface between the mastic and the aggregate. In the presence of voids, they ‘jump’ from one void to the closest void. Water expansion is modelled by coupling Peridynamics with repulsive forces in the context of Discrete Multiphysics. Freezing water expands against the voids’ internal surface, building tension in the material. A network of cracks forms in the asphalt, weakening its mechanical properties. The proposed methodology provides a computational tool for generating samples of ‘digital asphalt’ that can be tested to assess the asphalt properties under different operating conditions.

Statins are a class of drugs used to lower low-density lipoprotein cholesterol and are amongst the most prescribed medications worldwide. Most statins work as a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR), but statin intolerance from pleiotropic effects have been proposed to arise from non-specific binding due to poor enzyme-ligand sensitivity. Yet, research into the physicochemical properties of statins, and their interactions with off-target sites, has not progressed much over the past few decades. Here, we present a concise perspective on the role of statins in lowering serum cholesterol levels, and how their reported interactions with phospholipid membranes offer a crucial insight into the mechanism of some of the more commonly observed pleiotropic effects of statin administration. Lipophilicity, which governs hepatoselectivity, is directly related to the molecular structure of statins, which dictates interaction with and transport through membranes. The structure of statins is therefore a clinically important consideration in the treatment of hypercholesterolaemia. This review integrates the recent biophysical studies of statins with the literature on the physiological effects and provides new insights into the mechanistic cause of statin pleiotropy, and prospective means of understanding the cholesterol-independent effects of statins.

The objectives of this study were to evaluate the effects of daily top-dressing (individually feeding on the top of the total mixed ration) with rumen-protected methionine (RPM) from 30 ± 3 until 126 ± 3 Days in milk on productive and reproductive performance in lactating dairy cows. A total of 309 lactating dairy Holstein cows (138 primiparous and 171 multiparous) were randomly assigned to treatment diets containing either RPM (21.2 g of RPM + 38.8 g of dried distillers grain; 2.34% Methionine [Met] of metabolizable protein [MP]) or Control (CON; 60 g of dried distillers grain; 1.87% Met of MP). Plasma amino acids were evaluated at the time of artificial insemination (AI) and near pregnancy diagnosis. Milk production and milk composition were evaluated monthly. Pregnancy was diagnosed on Day 28 (by Pregnancy-specific protein B [PSPB]), 32, 47, and 61 (by ultrasound) and sizes of embryonic and amniotic vesicle were determined by ultrasound on Day 33 after AI. Feeding RPM increased plasma Met at 6, 9, 12, and 18 hours after top-dressing with a peak at 12 hours (52.4 vs 26.0 μM; P < 0.001) and returned to basal by 24 hours. Cows fed RPM had a small increase in milk protein percentage (3.08 vs 3.00%; P = 0.04) with no differences on milk yield and milk protein yield. Additionally, in multiparous cows, RPM feeding increased milk protein (3.03 vs 2.95%; P = 0.05) and fat (3.45 vs 3.14%; P = 0.01) percentages, although no effects were observed in primiparous cows. In multiparous cows fed RPM, pregnancy loss was lower between Days 28 to 61 (19.6 [10/51] vs. 6.1% [3/49]; P = 0.03) or between Days 32 to 61 (8.9 [4/45] vs. 0 [0/0] %; P = 0.03), although, there was no effect of treatment on pregnancy loss in primiparous cows. Consistent with data on pregnancy loss, RPM feeding increased embryonic abdominal diameter (P = 0.01) and volume (P = 0.009) and amniotic vesicle volume (P = 0.04) on Day 33 of pregnancy in multiparous cows but had no effect on embryonic size in primiparous cows. Thus, the increase in plasma Met concentrations after feeding RPM was sufficient to produce a small increase in milk protein percentage and to improve embryonic size and pregnancy maintenance in multiparous cows. Further studies are needed to confirm these responses and understand the biological mechanisms that underlie these responses as well as the timing and concentrations of circulating Met that are needed to produce this effect.

The road transportation sector is responsible for around 25% of total man-made CO2 emissions worldwide. Considerable efforts are therefore underway to reduce these emissions using several approaches, including improved vehicle technologies, traffic management and changing driving behaviour. Detailed traffic and emissions models are used extensively to assess the potential effects of these measures. However, if the input and calibration data are not sufficiently detailed there is an inherent risk that the results may be inaccurate. This article presents the use of Floating Car Data to derive useful speed and acceleration values in the process of traffic model calibration as a means of ensuring more accurate results when simulating the effects of particular measures. The data acquired includes instantaneous GPS coordinates to track and select the itineraries, and speed and engine performance extracted directly from the on-board diagnostics system. Once the data is processed, the variations in several calibration parameters can be analyzed by comparing the base case model with the measure application scenarios. Depending on the measure, the results show changes of up to 6.4% in maximum speed values, and reductions of nearly 15% in acceleration and braking levels, especially when eco-driving is applied.

Este artigo tece considerações sobre o tema da adolescência como uma fase única na vida, na qual a autonomia ganha cada vez mais força. O objetivo do estudo é discutir as implicações éticas da pesquisa epidemiológica, clínica ou farmacológica com os adolescentes, abordando aspectos relacionados ao seu desenvolvimento psicológico, social e moral. Ao final, serão revisados os principais conceitos e guidelines aplicáveis àqueles diferentes tipos de pesquisas.

This review identifies the ways in which tethered bilayer lipid membranes (tBLMs) can be used for the identification of the actions of antimicrobials against lipid bilayers. Much of the new research in this area has originated, or included researchers from, the southern hemisphere, Australia and New Zealand in particular. More and more, tBLMs are replacing liposome release assays, black lipid membranes and patch-clamp electrophysiological techniques because they use fewer reagents, are able to obtain results far more quickly and can provide a uniformity of responses with fewer artefacts. In this work, we describe how tBLM technology can and has been used to identify the actions of numerous antimicrobial agents.

Today’s dairies are growing rapidly, with increasing dependence on Latino immigrant workers. This requires new educational strategies for improving milk quality and introduction to state-of-the-art dairy farming practices. It also creates knowledge gaps pertaining to the health of animals and workers, mainly due to lack of time and language barriers. Owners, managers and herdsmen assign training duties to more experienced employees, which may not promote ‘best practices’ and may perpetuate bad habits. A comprehensive and periodic training program administered by qualified personnel is currently needed and will enhance the sustainability of the dairy industry. Strategic management and employee satisfaction will be achieved through proper training in the employee’s language, typically Spanish. The training needs to address not only current industry standards but also social and cultural differences. An innovative training course was developed following the same structure used by the engineering and construction industries, giving farm workers basic understanding of animal care and handling, cow comfort and personal safety. The Dairy Tool Box Talks program was conducted over a ten week period with nine 30-minute sessions according to farm’s various employee work shifts. Bulk milk bacterial counts and somatic cell count were used to evaluate milk quality on the three dairy farms participating in the program.Dairy Tool Box Talks resulted in a general sense of employee satisfaction, significant learning outcomes, and enthusiasm about the topics covered. We conclude this article by highlighting the importance of educational programs aimed at improving overall cross-cultural training.

BackgroundPerturbed balance between NO and O2•−. (ie, NO/redox imbalance) is central in the pathobiology of diabetes‐induced vascular dysfunction. We examined whether stimulation of β3 adrenergic receptors (β3 ARs), coupled to endothelial nitric oxide synthase (eNOS) activation, would re‐establish NO/redox balance, relieve oxidative inhibition of the membrane proteins eNOS and Na+‐K+ (NK) pump, and improve vascular function in a new animal model of hyperglycemia. Methods and ResultsWe established hyperglycemia in male White New Zealand rabbits by infusion of S961, a competitive high‐affinity peptide inhibitor of the insulin receptor. Hyperglycemia impaired endothelium‐dependent vasorelaxation by “uncoupling” of eNOS via glutathionylation (eNOS‐GSS) that was dependent on NADPH oxidase activity. Accordingly, NO levels were lower while O2•− levels were higher in hyperglycemic rabbits. Infusion of the β3 AR agonist CL316243 (CL) decreased eNOS‐GSS, reduced O2•−, restored NO levels, and improved endothelium‐dependent relaxation. CL decreased hyperglycemia‐induced NADPH oxidase activation as suggested by co‐immunoprecipitation experiments, and it increased eNOS co‐immunoprecipitation with glutaredoxin‐1, which may reflect promotion of eNOS de‐glutathionylation by CL. Moreover, CL reversed hyperglycemia‐induced glutathionylation of the β1 NK pump subunit that causes NK pump inhibition, and improved K+‐induced vasorelaxation that reflects enhancement in NK pump activity. Lastly, eNOS‐GSS was higher in vessels of diabetic patients and was reduced by CL, suggesting potential significance of the experimental findings in human diabetes. Conclusionsβ3 AR activation restored NO/redox balance and improved endothelial function in hyperglycemia. β3 AR agonists may confer protection against diabetes‐induced vascular dysfunction.