The goal of this research was to evaluate the microclimate (temperature, relative humidity and ECI-enthalpy comfort index) of commercial loads of broiler chickens at different transport distances: ...Dist15 (15 km on average) and Dist90 (90 km on average) in the summer and winter seasons and their effects on the production parameters body weight difference (BWD), mortality (%) and bruising prevalence (%). Twelve broiler loads were monitored using dataloggers to record temperature and humidity, with a total of 24 target crates per load. The experiment followed a factorial design 2 seasons (rainy and dry) × 2 distances (Dist15 and Dist90) with a randomized complete block arrangement, 3 sexes (all males, all females, or mixed shipments) and one shipment per combination. BWD had a heterogeneous distribution throughout the load, and this distribution was not significantly correlated with the mean ECI measured during transport at 12 positions along the load. In terms of comfort, summer is the most critical period for broiler transport. In the interaction between rainy season and Dist90, the highest ECI was scored in the lethal zone (where physiological mechanisms are not enough to control body temperature). Mortality during the rainy season was not significantly different between distances. However, during the dry season, mortality was twice as high as broilers that travelled for 15 km. The prevalence of bruising on carcasses was not affected by the interaction between season and distance. As we know, broiler chicken performance, during transport, can be also related to road conditions, being hard to evaluate the real impact of seasons and distances on animal welfare. Load microclimate can compromise broiler chicken welfare during transport and it does not necessary reflect significant losses pre and post-slaughter.
The adulteration of whiskey with analgesics and sedation drugs has been a common practice to prevent hangover the following day and promote loss of consciousness. In both situations, the portable and ...low cost detection platforms are of paramount importance for forensic investigations. This report describes the use of electrochemical paper‐based analytical devices (ePADs) fabricated by pencil drawing for detecting metamizole, paracetamol and midazolam maleate in whiskey. Different types of paper substrates and graphite pencils were initially characterized with ferrocyanide. The best results were achieved using vegetal paper and Aquarelle/6B pencils. ePADs revealed a decrease in current signal indicating a short lifetime, thus limiting their use to disposable sensors. Despite the short lifetime, the graphite pencil ePADs revealed good electrochemical reproducibility (RSD=3.3 %). The forensic feasibility of the proposed ePADs was demonstrated through the analysis of metamizole and paracetamol in whiskey. The limit of detection (LOD) achieved for paracetamol and metamizole were 45 and 20 mg L−1, respectively. ePADs were also tested to detect midazolam maleate in whiskey. The signal recorded exhibited linear correlation in a wide concentration range (25–1000 mg L−1) and a LOD of ca. 5 mg L−1. Considering the disposability and operational simplicity, ePADs offer a good strategy for detecting adulterations in alcoholic beverages at the point‐of‐need.
This study describes the development of a new electrochemical paper-based analytical device (ePAD) on alumina sandpaper substrate through a pencil-drawing process for square wave voltammetry ...measurements of midazolam maleate used as a “date rape drug” in beverages. The proposed ePAD was assembled on a reusable 3D printed holder to delimit its geometric area and ensure better robustness. The ePAD was characterized by scanning electron microscopy, cyclic voltammetry, electrochemical impedance spectroscopy and Raman spectroscopy. The direct drawing of ePADs on sandpaper platforms through a graphite pencil has offered suitable repeatability (RSD = 1.0%) and reproducibility (RSD = 4.0%) using Fe(CN)64– as redox probe. The proposed ePAD provided linear behaviour in the midazolam maleate concentration range between 2.5 and 150 mg L−1 and a limit of detection of 2.0 mg L−1. The feasibility of the ePAD for forensic application was successfully demonstrated through the detection of midazolam in different beverages (water, beer, liquor, and vodka). The intended application revealed low interference of other compounds present in beverages. Based on the achieved results, the proposed ePAD has offered great accuracy with no statistical difference at 95% confidence level from the data recorded by high performance liquid chromatography. The operational simplicity and the robustness ensured by the assembling on a reusable 3D printed holder make the ePAD drawn on sandpaper platform a powerful and promising analytical tool for the analysis of “date rape drugs” opening new possibilities for on-site forensic investigations.
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•Sandpaper substrate was explored to fabricate electrochemical devices through pencil drawing protocol.•ePADs were assembled on a reusable 3D-printed holder and covered with PDMS to define the geometric area.•The forensic feasibility was demonstrated through the detection of date rape drug.•The achieved results revealed good agreement with the data recorded using HPLC.•The proposed assembled device offered operational simplicity and an environmentally friendly strategy.
Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson’s disease (PD) suggesting that a sustained neuroinflammation ...exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH
+
) and microglia markers (Iba-1
+
; CD68
+
) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68
+
/ Iba-1
+
cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions.
Graphical Abstract
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.
Acid sphingomyelinase deficiency (ASMD) is a lysosomal disorder caused by deficiency of acid sphingomyelinase (ASM) leading to the accumulation of sphingomyelin (SM) in a variety of cell types. ...Lysosphingomyelin (LysoSM) is the de-acetylated form of SM and it has been shown as a biomarker for ASMD in tissues, plasma, and dried blood spots (DBS) and lysosphingomyelin-509 (LysoSM509) is the carboxylated analogue of LysoSM. High levels of Lysosphingomyelin 509 (LysoSM509) have also been shown in ASMD patients. In this study, we report the utility of the quantification of LysoSM and LysoSM509 in DBS of patients from Latin America with ASMD by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).
DBS samples from 14 ASMD patients were compared with 15 controls, and 44 general newborns. All patients had their diagnosis confirmed by the quantification of ASM and the measurement of the activity of chitotriosidase. All patients had significantly higher levels of lysoSM and lysoSM509 compared to controls and general newborns.
The quantification of lysosphingolipids in DBS is a valuable tool for the diagnosis of ASMD patients and lysoSM can be useful in the differential diagnosis with NPC. This method is also valuable in the ASMD newborn screening process.
Physical principles and laws determine the set of possible organismal phenotypes. Constraints arising from development, the environment, and evolutionary history then yield workable, integrated ...phenotypes. We propose a theoretical and practical framework that considers the role of changing environments. This ‘ecomechanical approach’ integrates functional organismal traits with the ecological variables. This approach informs our ability to predict species shifts in survival and distribution and provides critical insights into phenotypic diversity. We outline how to use the ecomechanical paradigm using drag-induced bending in trees as an example. Our approach can be incorporated into existing research and help build interdisciplinary bridges. Finally, we identify key factors needed for mass data collection, analysis, and the dissemination of models relevant to this framework.
All organisms must comply with physical laws, which place rigid or hard constraints on survival and reproduction. Ecomechanics is the expression of that interplay, and assumes a central role when considering organismal development, ecology, and evolution.How organisms will respond to changes in the environment, such as human-mediated climate change, will depend strongly on ecomechanics.Functional traits are commonly used to investigate the consequences of ecological variation. Ecomechanical models that incorporate functional traits and environmental variables are key to deciphering the rules of life and expand upon functional trait studies.The use of the ecomechanical framework is illustrated using multiple examples (e.g., wind-induced bending mechanics in trees and gecko adhesion in the real world). We emphasize safety factors as a key metric when assessing the evolution of form and performance. Biologists can apply our framework to many other systems.We offer suggestions for constructing and tailoring the data pipeline for future ecomechanical models to enhance their availability and utility for various disciplines.
The lack of precision to predict service performance through load indices may lead to wrong decisions regarding the use of web services, compromising service performance and raising platform cost ...unnecessarily. This paper presents experimental studies to qualify the behaviour of load indices in the web service context. The experiments consider three services that generate controlled and significant server demands, four levels of workload for each service and six distinct execution scenarios. The evaluation considers three relevant perspectives: the capability for representing recent workloads, the capability for predicting near-future performance and finally stability. Eight different load indices were analysed, including the JMX Average Time index (proposed in this paper) specifically designed to address the limitations of the other indices. A systematic approach is applied to evaluate the different load indices, considering a multiple linear regression model based on the stepwise-AIC method. The results show that the load indices studied represent the workload to some extent; however, in contrast to expectations, most of them do not exhibit a coherent correlation with service performance and this can result in stability problems. The JMX Average Time index is an exception, showing a stable behaviour which is tightly-coupled to the service runtime for all executions. Load indices are used to predict the service runtime and therefore their inappropriate use can lead to decisions that will impact negatively on both service performance and execution cost.
Maturity‐Onset Diabetes of the Young (MODY) type 4 or
PDX1
‐MODY is a rare form of monogenic diabetes caused by heterozygous variants in
PDX1
. Pancreatic developmental anomalies related to
PDX1
are ...reported only in neonatal diabetes cases. Here, we describe dorsal pancreatic agenesis in 2 patients with
PDX1
‐MODY. The proband presented with diabetes since 14 years of age and maintained regular glycemic control with low doses of basal insulin and detectable C‐peptide levels after 38 years with diabetes. A diagnosis of MODY was suspected. Targeted next‐generation sequencing identified a heterozygous variant in
PDX1
: c.188delC/p.Pro63Argfs*60. Computed tomography revealed caudal pancreatic agenesis. Low fecal elastase indicated exocrine insufficiency. His son had impaired glucose tolerance, presented similar pancreatic agenesis, and harbored the same allelic variant. The unusual presentation in this Brazilian family enabled expansion upon a rare disease phenotype, demonstrating the possibility of detecting pancreatic malformation even in cases of
PDX1
‐related diabetes diagnosed after the first year of life. This finding can improve the management of MODY4 patients, leading to precocious investigation of pancreatic dysgenesis and exocrine dysfunction.
The relationship established between Leishmania infantum and the vertebrate host can lead to a self-healing infection or to the manifestation of visceral leishmaniasis, a chronic systemic infection ...associated with high rates of mortality. We hypothesized that regulatory cytokines, such as interleukin-27 (IL-27), play a role in susceptibility to L. infantum infection. IL-27 is a heterodimeric cytokine composed of IL-27p28 and EBi3 subunits which, when combined, bind to IL-27R, leading to STAT-1 and -3 activation, playing a role in the regulation of the immune response. We observed in this work that IL-27 regulates the Th1/Th17 profiles in a mouse model of visceral leishmaniasis (VL) caused by L. infantum We showed here that the pathogen recognition by endosomal Toll-like receptors triggers a type I interferon (IFN) response, which acts through the type I IFN receptor and interferon regulatory factor 1 to induce IL-27 production by macrophages. Furthermore, IL-27 plays a major regulatory role in vivo, because Ebi3(-/-) mice can efficiently control parasite replication despite reduced levels of IFN-γ compared to wild-type mice. On the other hand, the absence of Ebi3 leads to exacerbated IL-17A production in the infected organs as well as in a coculture system, suggesting a direct regulatory action of IL-27 during L. infantum infection. As a consequence of exacerbated IL-17A in Ebi3(-/-) mice, a greater neutrophil influx was observed in the target organs, playing a role in parasite control. Thus, this work unveiled the molecular steps of IL-27 production after L. infantum infection and demonstrated its regulatory role in the IL-17A-neutrophil axis.
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