In vivo MRI and PET imaging in a translational ILD mouse model expressing non-resolving fibrosis and bronchiectasis-like pathology after repeated systemic exposure to bleomycin.

Drug-induced interstitial lung disease (ILD) is crucial to detect early to achieve the best treatment outcome. Optimally, non-invasive imaging biomarkers can be used for early detection of disease progression and treatment follow-up. Therefore, reliable in vivo models are warranted in new imaging biomarker development to accelerate better-targeted treatment options. Single-dose bleomycin models have, for a long time, served as a reference model in fibrosis and lung injury research. Here, we aimed to use a clinically more relevant animal model by systemic exposure to bleomycin and assessing disease progression over time by combined magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging. Methods: C57BL/6 mice received bleomycin (i.p. 35iU/kg) or saline as control twice per week for 4 weeks. Mice were monitored until 2 weeks after cessation of bleomycin administration (w4 + 1 and w4 + 2), referred to as the resting period. MRI scans were performed in weeks 3 and 4 and during the resting weeks. [18F]FDG-PET was performed at the last week of dosing (w4) and 2 weeks after the last dosing (w4 + 2). Lung tissue sections were stained with Masson's trichrome and evaluated by modified Ashcroft scoring. Lung volume and lesion volumes were assessed using MRI, as well as 3D mapping of the central airways. Results and discussion: Bleomycin-challenged mice showed increased lung weights (p < 0.05), while total lung volume was unchanged (w4 and onward). Histology analysis demonstrated fibrotic lesions emanating from the distal parts of the lung. Fibrosis progression was visualized by MRI with significantly increased high signal in bleomycin-exposed lungs compared to controls (p < 0.05). In addition, a significant increase in central airway diameter (p < 0.01) was displayed in bleomycin-exposed animals compared to controls and further continued to dilate as the disease progressed, comparing the bleomycin groups over time (p < 0.05-0.001). Lung [18F]FDG uptake was significantly elevated in bleomycin-exposed mice compared to controls (p < 0.05). Conclusion: Non-invasive imaging displayed progressing lesions in the lungs of bleomycin-exposed mice, using two distinct MRI sequences and [18F]FDG-PET. With observed fibrosis progression emanating from distal lung areas, dilation of the central airways was evident. Taken together, this chronic bleomycin-exposure model is translationally more relevant for studying lung injury in ILD and particularly in the context of DIILD.

Improving Bioprocess Conditions for the Production of Prodigiosin Using a Marine Serratia rubidaea Strain.

The enormous potential attributed to prodigiosin regarding its applicability as a natural pigment and pharmaceutical agent justifies the development of sound bioprocesses for its production. Using a Serratia rubidaea strain isolated from a shallow-water hydrothermal vent, optimization of the growth medium composition was carried out. After medium development, the bacterium temperature, light and oxygen needs were studied, as was growth inhibition by product concentration. The implemented changes led to a 13-fold increase in prodigiosin production in a shake flask, reaching 19.7 mg/L. The conditions allowing the highest bacterial cell growth and prodigiosin production were also tested with another marine strain: S. marcescens isolated from a tide rock pool was able to produce 15.8 mg/L of prodigiosin. The bioprocess with S. rubidaea was scaled up from 0.1 L shake flasks to 2 L bioreactors using the maintenance of the oxygen mass transfer coefficient (kLa) as the scale-up criterion. The implemented parameters in the bioreactor led to an 8-fold increase in product per biomass yield and to a final concentration of 293.1 mg/L of prodigiosin in 24 h.

Influence of preventive remineralizing techniques on surface roughness and volume loss of dentin submitted to erosive and/or abrasive challenges.

Background: The objective this study was to evaluate the influence of preventive remineralizing techniques on surface roughness and volume loss of dentin submitted to erosive and/or abrasive challenges. Material and Methods: One hundred and eighty specimens of bovine root dentin were made; half of each was isolated (without treatment - WT) and half was subjected to the following remineralizing techniques: fluoride varnish (FV); Regenerate Boosting Serum® (RBS); Er,Cr:YSGG laser (L); fluoride varnish+laser (FV+L); Regenerate Boosting Serum®+laser (RBS+L). The specimens were submitted to erosive, abrasive and erosive followed by abrasive challenge. Erosion was carried out for 5 minutes, twice a day for 10 days. Abrasion was performed with an electric toothbrush and slurry solution for 60 seconds. The evaluation was performed by confocal laser scanning microscopy. Analysis of variance and Tukey tests were used for surface roughness; volume loss comparison was performed using the Kruskal-Wallis test and Dunn's post-hoc (p<0.05). Results: There was no statistically significant difference in the surface roughness of the reference area in relation to the areas submitted to different types of treatment and challenges (p>0.05). Regarding volume loss, the untreated group submitted to erosive/abrasive challenges showed greater percentage of volume loss compared to the other groups (p<0.05). Conclusions: It is concluded that preventive remineralizing techniques are effective in maintaining dentin volume after erosive/abrasive challenges. Key words:YSGG lasers, Dentin, Erosion, Tooth Abrasion.

Early Intensive Neurorehabilitation in Traumatic Peripheral Nerve Injury-State of the Art.

Traumatic nerve injuries are common lesions that affect several hundred thousand humans, as well as dogs and cats. The assessment of nerve regeneration through animal models may provide information for translational research and future therapeutic options that can be applied mutually in veterinary and human medicine, from a One Health perspective. This review offers a hands-on vision of the non-invasive and conservative approaches to peripheral nerve injury, focusing on the role of neurorehabilitation in nerve repair and regeneration. The peripheral nerve injury may lead to hypersensitivity, allodynia and hyperalgesia, with the possibility of joint contractures, decreasing functionality and impairing the quality of life. The question remains regarding how to improve nerve repair with surgical possibilities, but also considering electrical stimulation modalities by modulating sensory feedback, upregulation of BDNF, GFNF, TrKB and adenosine monophosphate, maintaining muscle mass and modulating fatigue. This could be improved by the positive synergetic effect of exercises and physical activity with locomotor training, and other physical modalities (low-level laser therapy, ultrasounds, pulsed electromagnetic fields, electroacupuncture and others). In addition, the use of cell-based therapies is an innovative treatment tool in this field. These strategies may help avoid situations of permanent monoplegic limbs that could lead to amputation.

Novel yeast-based biosensor for environmental monitoring of tebuconazole.

Due to increasing demand for high and stable crop production, human populations are highly dependent on pesticide use for growing and storing food. Environmental monitoring of these agrochemicals is therefore of utmost importance, because of their collateral effects on ecosystem and human health. Even though most current-use analytical methods achieve low detection limits, they require procedures that are too complex and costly for routine monitoring. As such, there has been an increased interest in biosensors as alternative or complementary tools to streamline detection and quantification of environmental contaminants. In this work, we developed a biosensor for environmental monitoring of tebuconazole (TEB), a common agrochemical fungicide. For that purpose, we engineered S. cerevisiae cells with a reporter gene downstream of specific promoters that are expressed after exposure to TEB and characterized the sensitivity and specificity of this model system. After optimization, we found that this easy-to-use biosensor consistently detects TEB at concentrations above 5 µg L-1 and does not respond to realistic environmental concentrations of other tested azoles, suggesting it is specific. We propose the use of this system as a complementary tool in environmental monitoring programs, namely, in high throughput scenarios requiring screening of numerous samples. KEY POINTS: • A yeast-based biosensor was developed for environmental monitoring of tebuconazole. •The biosensor offers a rapid and easy method for tebuconazole detection ≥ 5 µg L-1. •The biosensor is specific to tebuconazole at environmentally relevant concentrations.

The Role of Early Rehabilitation and Functional Electrical Stimulation in Rehabilitation for Cats with Partial Traumatic Brachial Plexus Injury: A Pilot Study on Domestic Cats in Portugal.

This prospective observational cohort pilot study included 22 cats diagnosed with partial traumatic brachial plexus injury (PTBPI), aiming to explore responses to an early intensive neurorehabilitation protocol in a clinical setting. This protocol included functional electrical stimulation (FES), locomotor treadmill training and kinesiotherapy exercises, starting at the time with highest probability of nerve repair. The synergetic benefits of this multimodal approach were based on the potential structural and protective role of proteins and the release of neurotrophic factors. Furthermore, FES was parametrized according to the presence or absence of deep pain. Following treatment, 72.6% of the cats achieved ambulation: 9 cats within 15 days, 2 cats within 30 days and 5 cats within 60 days. During the four-year follow-up, there was evidence of improvement in both muscle mass and muscle weakness, in addition to the disappearance of neuropathic pain. Notably, after the 60 days of neurorehabilitation, 3 cats showed improved ambulation after arthrodesis of the carpus. Thus, early rehabilitation, with FES applied in the first weeks after injury and accurate parametrization according to the presence or absence of deep pain, may help in functional recovery and ambulation, reducing the probability of amputation.

Mineral profile and histopathological findings in the liver of white-lipped frog (Leptodactylidae) from the morphoclimatic domain of the Caatingas, Brazil.

This study aimed to investigate the mineral profile and histopathological findings in the liver of Leptodactylus macrosternum (white-lipped frog) and to assess the association between melanomacrophage areas and hepatic fungal granuloma with several factors such as weight, snout-cloacal length, sex, hepatosomatic index, season (dry and rainy), and condition factor K. A total of 135 frogs of different ages were collected from three areas in the city of Petrolina, Pernambuco, with varying land use (conventional agriculture, organic agriculture, and Caatinga stricto sensu). The liver of all specimens exhibited changes such as granulomatous lesions, inflammatory cell infiltrate, blood vessel congestion, and sinusoid dilation. The melanomacrophage areas were influenced by weight, snout-cloacal length, and hepatosomatic index. Our findings revealed a positive correlation between body size (weight and snout-cloacal length) and melanomacrophage/hepatic granuloma, while the hepatosomatic index showed a negative relationship. For the condition factor K, only age presents relationship. Eleven elements were quantified for the mineral profile, with aluminum (Al), iron (Fe), and zinc (Zn) being the most abundant in both liver and muscle. Although the histopathological findings and mineral profile of the liver and muscle in this study indicate an effect on the health of L. macrosternum in different collection areas, confirming the relationship between environmental characteristics and these findings requires future studies. Furthermore, long-term studies would be necessary to allow the monitoring of all stages of development of these populations, from tadpoles to adults, for a better evaluation of these effects in L. macrosternum.

Isolation and Characterization of a Serratia rubidaea from a Shallow Water Hydrothermal Vent.

Microbial life present in the marine environment has to be able to adapt to rapidly changing and often extreme conditions. This makes these organisms a putative source of commercially interesting compounds since adaptation provides different biochemical routes from those found in their terrestrial counterparts. In this work, the goal was the identification of a marine bacterium isolated from a sample taken at a shallow water hydrothermal vent and of its red product. Genomic, lipidomic, and biochemical approaches were used simultaneously, and the bacterium was identified as Serratia rubidaea. A high-throughput screening strategy was used to assess the best physico-chemical conditions permitting both cell growth and production of the red product. The fatty acid composition of the microbial cells was studied to assess adaptation at the lipid level under stressful conditions, whilst several state-of-the-art techniques, such as DSC, FTIR, NMR, and Ultra-High Resolution Qq-Time-of-Flight mass spectrometry, were used to characterize the structure of the pigment. We hypothesize that the pigment, which could be produced by the cells up to 62 °C, is prodigiosin linked to an aliphatic compound that acts as an anchor to keep it close to the cells in the marine environment.

Effect of Uncaria tomentosa aqueous extract on the response to palmitate-induced lipotoxicity in cultured skeletal muscle cells.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is frequently associated with dyslipidemia, which corresponds to the increase in the triglycerides and fatty acid concentrations in tissues, such as the skeletal muscle. Also, T2DM molecular mechanism involves increasing in reactive oxygen species (ROS) production and oxidative stress. The use of herbal medicines such as Uncaria tomentosa (Ut) has been proposed as an auxiliary treatment for patients with T2DM. In this study, it was evaluated the effect of Ut aqueous extract on cell viability and ROS production, in skeletal myoblasts from C2C12 lineage exposed to the free fatty acid palmitate (PA). METHODS: Cells were incubated with PA in different concentrations ranging from 10 to 1000 µM, for 24 or 48 h, for cytotoxicity assay. Cell death, DNA fragmentation and ROS production assays were performed in cell cultures incubated with PA for 24 h, in the pre (preventive condition) or post treatment (therapeutic condition) with 250 µg/ml Ut aqueous extract, for 2 or 6 h. Cell death was evaluated by MTT method or flow cytometry. ROS generation was measured by fluorescence spectroscopy using the DCFDA probe. RESULTS: Cell viability was reduced to approximately 44% after the incubation with PA for 24 h from the concentration of 500 µM. In the incubation of cells with 500 µM PA and Ut extract for 6 h, in both conditions (preventive or therapeutic), it was observed an increase of 27 and 70% in cell viability respectively, in comparison to the cultures incubated with only PA. Also, the incubation of cultures with 500 µM PA, for 24 h, increased 20-fold the ROS formation, while the treatment with Ut extract, for 6 h, both in the preventive or therapeutic conditions, promoted decrease of 21 and 55%, respectively. CONCLUSION: The Ut extract was efficient in promoting cell protection against PA lipotoxicity and ROS generation, potentially preventing oxidative stress in C2C12 skeletal muscle cells. Since T2DM molecular mechanism involves oxidative stress condition and it is often associated with dyslipidemia and fatty acid accumulation in muscle tissue, these results open perspectives for the use of Ut as an auxiliary strategy for T2DM management.

"Does Physical Exercise Promote Health Benefits for Diabetic Patients during the COVID-19 Pandemic?": A Systematic Review.

Patients affected by COVID-19 are prone to facing disorders in multiple systems and organs, which can lead to deleterious diseases; in addition, people with pre-existing diseases may be more prone to the worst outcomes, and the most vulnerable are patients with type 1 and type 2 diabetes mellitus. The aim of this systematic review was to evaluate the effects of physical activity and/or physical exercise prescribed to individuals with diabetes on the maintenance of plasma glucose and glycated hemoglobin during the COVID-19 pandemic. Studies were found by searching PubMed, SCOPUS, Embase, Web of Science, SciELO, LILACS, SportDiscus, Bireme/BVS and Google Scholar databases. The inclusion criteria were articles that addressed only patients with type 1 or type 2 diabetes (T1D and T2D) who had evaluated the level of physical activity or physical exercise and described the effects on plasma glucose and/or glycated hemoglobin in cross-sectional, retrospective, and observational studies, meeting the main criteria established by GRADE. The PICO and GRADE strategies were used to select and assess the methodological quality of studies. Two reviewers searched and selected the articles in databases independently and blindly, during which oppositions and disagreements about the inclusion of articles were discussed and resolved by a third reviewer. Evidence corroborates that levels of physical activity were reduced due to the lockdown, leading to increased body weight and worse glycemic control. On the other hand, individuals with diabetes mellitus (DM) (T1D and T2D) who maintained and/or increased levels of physical activity or physical exercise showed reduced plasma glucose and glycated hemoglobin (HbA1c) levels. Adequate levels of physical exercise and physical activity are beneficial for glucose and HbA1c control in diabetic patients (type 1 or type 2). In addition, maintaining adequate levels of physical activity can contribute to reducing health problems when these patients are infected with COVID-19.

Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD.

Cell replacement therapies for Parkinson's disease (PD) based on transplantation of pluripotent stem cell-derived dopaminergic neurons are now entering clinical trials. Here, we present quality, safety, and efficacy data supporting the first-in-human STEM-PD phase I/IIa clinical trial along with the trial design. The STEM-PD product was manufactured under GMP and quality tested in vitro and in vivo to meet regulatory requirements. Importantly, no adverse effects were observed upon testing of the product in a 39-week rat GLP safety study for toxicity, tumorigenicity, and biodistribution, and a non-GLP efficacy study confirmed that the transplanted cells mediated full functional recovery in a pre-clinical rat model of PD. We further observed highly comparable efficacy results between two different GMP batches, verifying that the product can be serially manufactured. A fully in vivo-tested batch of STEM-PD is now being used in a clinical trial of 8 patients with moderate PD, initiated in 2022.

Spinal shock in severe SCI dogs and early implementation of intensive neurorehabilitation programs.

Spinal shock is complex, paradoxical with sudden presentation, possibly leading to a guarded prognosis. Thus, it is suggested the need for early implementation of intensive neurorehabilitation. This prospective controlled blinded cohort study aims to understand the implication of spinal shock in neurorehabilitation of severe SCI dogs and the importance of its evaluation thought a spinal shock scale (SSS). 371 dogs were randomized by stratification according the presence of spinal shock in the SG (n = 245) or CG (n = 126). The SSS, a punctuation scale (0-7), was evaluated at admission and each 6 h for 3 days, each day for 15 days, each week for 6 weeks, each month until 3 months, followed by 3 monthly follow-ups. All dogs had similar land and underwater treadmill training with functional electrical stimulation. Observational dataset allowed an approximate level of power (1-ß) of 0.90 and an α (Type I error) of 0.01, with a total of 11,088 SSS observations between two blinded observers and 18% of disagreement. 75% of the dogs were admitted in 24-48 h after injury, allowing early detection of spinal shock, and dogs admitted at 72 h with SSS ≥ 4 were not able to achieve ambulation. Regarding ambulation rate, there was a significant difference between groups, with 66.9% of ambulation in the SG and 97.6% in the CG. Also, there was a difference in regard to time until ambulation, with a mean of 31.57 days for the SG and 23.02 for the CG. The SSS estimated marginal means had an exponential decrease within the first 6 h, followed by a slower decrease, but always faster in spinal shock dogs diagnosed with non-compressive myelopathies. Thus, early intensive neurorehabilitation in dogs after severe SCI may benefit from SSS classifications at admission and during treatment to establish different therapeutic protocols according to each patient's needs, especially in deep pain negative dogs.

Linking centennial scale anthropogenic changes and sedimentary records as lessons for urban coastal management.

Coastal eutrophication and urban flooding are increasingly important components of global change. Although increased seawater renewal by barrier openings and channelizing are common mitigation measures in coastal lagoons worldwide, their effects on these ecosystems are not fully understood. Here, we evaluated the relationships between human interventions in the watershed, artificial connections to the sea, and the sediment burial rates in an urban coastal lagoon (Maricá lagoon, Southeastern Brazil). Sediment accretion along with nutrient and carbon burial rates were determined in two sediment cores representing the past ∼120 years (210Pb dating) and associated with anthropogenic changes as indicated by historical records and geoinformation analyses. Lagoon infilling and eutrophication, expressed by the average sediment accretion, TP, TN, and OC burial rates, respectively, increased ∼9-18, 13-15, 11-14 and 11-12-fold from the earliest (<1950) to the most recent (2000-2017) period. These multi-proxy records confirm mechanistic links between deforestation, urbanization, and untreated sewage discharges. In addition, our findings reveal artificial connections to the sea may contribute to lagoonal eutrophication and infilling, particularly when not integrated with sewage treatment and forest conservation or reforestation in the watershed. Therefore, increased seawater renewal by physical interventions commonly considered as mitigation measures may in contrast cause severe degradation in coastal lagoons, causing harmful consequences that should be not neglected when implementing management practices.

A magnetic nanoparticle-based microfluidic device fabricated using a 3D-printed mould for separation of Escherichia coli from blood.

Herein, A microfluidic device is described, produced with a 3D-printed master mould that rapidly separates and concentrates Escherichia coli directly from whole blood samples, enabling a reduction in the turnaround time of bloodstream infections (BSIs) diagnosis. Moreover, it promotes the cleansing of the blood samples whose complexity frequently hampers bacterial detection. The device comprises a serpentine mixing channel with two inlets, one for blood samples (spiked with bacteria) and the other for magnetic nanoparticles (MNPs) functionalized with a (bacterio)phage receptor-binding protein (RBP) with high specificity for E. coli. After the magnetic labelling of bacteria throughout the serpentine, the microchannel ends with a trapping reservoir where bacteria-MNPs conjugates are concentrated using a permanent magnet. The optimized sample preparation device successfully recovered E. coli (on average, 66%) from tenfold diluted blood spiked within a wide range of bacterial load (102 CFU to 107 CFU mL-1). The non-specific trapping, tested with Staphylococcus aureus, was at a negligible level of 12%. The assay was performed in 30 min directly from diluted blood thus presenting an advantage over the conventional enrichment in blood cultures (BCs). The device is simple and cheap to fabricate and can be tailored for multiple bacterial separation from complex clinical samples by using RBPs targeting different species. Moreover, the possibility to integrate a biosensing element to detect bacteria on-site can provide a reliable, fast, and cost-effective point-of-care device.

Biocatalysis of Steroids by Mycobacterium sp. in Aqueous and Organic Media.

Mycobacterium sp. can convert steroids such as ß-sitosterol, campesterol, and cholesterol, by selective side-chain cleavage and oxidation of the C3 hydroxyl group to a ketone, into key intermediates that can be easily functionalized to yield commercially interesting pharmaceutical products. In aqueous systems, the biocatalysis is limited by the low solubility of the steroids in water. Several strategies have been introduced to tackle this limitation, e.g., formation of cyclodextrin-steroid complexes and generation of aqueous microdispersions with steroid particle size in the range of hundreds of nanometers. Still, the introduction of an organic phase acting as a substrate and/or product reservoir is a well-established and relatively easy to implement strategy to overcome the sparing water solubility of steroid molecules. However, the organic phase has to be carefully chosen to prevent tampering with the activity/viability of microbial cells.In this chapter, we describe the methodology for the biocatalysis of ß-sitosterol to 4-androstene-3,17-dione (AD) and 1,4-androstadiene-3,17-dione (ADD), both in aqueous and organic:aqueous systems. In the latter case, both traditional organic solvents and green solvents are proposed.

In Vitro Antiprotozoal Activity of Hibiscus sabdariffa Extract against a Ciliate Causing High Mortalities in Turbot Aquaculture.

Philasterides dicentrarchi is an histophagous parasite that infects flatfish, namely turbot (Scophthalmus maximus), and cause significant losses in aquaculture units. The available measures for P. dicentrarchi control have limited efficiency, and some cause harm to fish. Hence, sustainable and natural control strategies are urgently needed. This study evaluated the in vitro bioactivity of the ethanol extract of Hibiscus sabdariffa calyces on P. dicentrarchi population growth rate (PGR), oxidative stress biomarkers (glutathione-S-transferases (GST), glutathione reductase (GR), glutathione peroxidase (GPx), total glutathione (TG) and catalase (CAT), neurotoxicity (acetylcholinesterase, AChE), activity and gene expression of proteases as major virulence factors. H. sabdariffa extract inhibited parasite PGR (IC50 = 1.57 mg mL-1), and caused significant changes in the activity of antioxidant enzymes (LOEC = 0.22 mg mL-1), especially GPx, TG, and CAT. The activity of proteases was also severely inhibited (IC50 = 0.76 mg mL-1), and gene expression of catepsin 90 and leishmanolysin proteases was downregulated. Organic acids and phenolic phytochemicals in hibiscus extract are potentially responsible for the antiprotozoal bioactivity herein determined. Therefore, H. sabdariffa extract can be a promising disease-control alternative against the ciliate proliferation, cellular defense mechanisms and pathogenicity. Still, its applicability in aquaculture settings, and potential effects on farmed fish, should be further elucidated.

Intensive neurorehabilitation and allogeneic stem cells transplantation in canine degenerative myelopathy.

Introduction: Degenerative myelopathy (DM) is a neurodegenerative spinal cord disease with upper motor neurons, with progressive and chronic clinical signs, similar to amyotrophic lateral sclerosis (ALS). DM has a complex etiology mainly associated with SOD1 gene mutation and its toxic role, with no specific treatment. Daily intensive rehabilitation showed survival time near 8 months but most animals are euthanized 6-12 months after clinical signs onset. Methods: This prospective controlled blinded cohort clinical study aims to evaluate the neural regeneration response ability of DM dogs subjected to an intensive neurorehabilitation protocol with mesenchymal stem cells (MSCs) transplantation. In total, 13 non-ambulatory (OFS 6 or 8) dogs with homozygous genotype DM/DM and diagnosed by exclusion were included. All were allocated to the intensive neurorehabilitation with MSCs protocol (INSCP) group (n = 8) or to the ambulatory rehabilitation protocol (ARP) group (n = 5), which differ in regard to training intensity, modalities frequency, and MSCs transplantation. The INSCP group was hospitalized for 1 month (T0 to T1), followed by MSCs transplantation (T1) and a second month (T2), whereas the ARP group was under ambulatory treatment for the same 2 months. Results: Survival mean time of total population was 375 days, with 438 days for the INSCP group and 274 for the ARP group, with a marked difference on the Kaplan-Meier survival analysis. When comparing the literature's results, there was also a clear difference in the one-sample t-test (p = 0.013) with an increase in time of approximately 70%. OFS classifications between groups at each time point were significantly different (p = 0.008) by the one-way ANOVA and the independent sample t-test. Discussion: This INSCP showed to be safe, feasible, and a possibility for a long progression of DM dogs with quality of life and functional improvement. This study should be continued.

The robot eyes don't have it. The presence of eyes on collaborative robots yields marginally higher user trust but lower performance.

Eye gaze is a prominent feature of human social lives, but little is known on whether fitting eyes on machines makes humans trust them more. In this study we compared subjective and objective markers of human trust when collaborating with eyed and non-eyed robots of the same type. We used virtual reality scenes in which we manipulated distance and the presence of eyes on a robot's display during simple collaboration scenes. We found that while collaboration with eyed cobots resulted in slightly higher subjective trust ratings, the objective markers such as pupil size and task completion time indicated it was in fact less comfortable to collaborate with eyed robots. These findings are in line with recent suggestions that anthropomorphism may be actually a detrimental feature of collaborative robots. These findings also show the complex relationship between human objective and subjective markers of trust when collaborating with artificial agents.

Is elevated blood glucose at admission associated with poor outcomes in hospitalized COVID-19 patients?

Objective: Hyperglycemia has been suggested as a risk factor for poor outcomes in coronavirus disease 2019 (COVID-19). The aim of our work was to evaluate the association between blood glucose levels at admission (BGA) and disease outcomes in hospitalized COVID-19 patients. Subjects and methods: Retrospective study including all adult COVID-19 patients admitted to a Portuguese hospital from March to August 2020 with BGA measurement. Subjects were categorized into two groups: BGA < 140 mg/dL and ≥ 140 mg/dL. Statistical analysis was performed using SPSSv26® (significance defined as p < 0.05). Results: We included 202 patients: median age 74 (60-86) years; 43.1% female; 31.2% with diabetes. The median BGA was 130.5 (108-158) mg/dL. When compared to normoglycemic, patients with BGA ≥ 140 mg/dL were older (p = 0.013), more vaccinated for influenza (p = 0.025) and had more comorbidities (hypertension, heart failure and peripheral arterial disease, p < 0.05). The last group presented higher leucocyte and neutrophile count, higher procalcitonin and prothrombin time, and lower lymphocyte count. Concerning prognosis, BGA ≥ 140 mg/dL was associated with higher rates of mechanical ventilation requirement and intensive care unit admission (p < 0.001), shock (p = 0.011), in-hospital mortality (p = 0.022) and 30-day mortality (p = 0.037). Considering only non-diabetic patients (n = 139), those with hyperglycemia presented higher rates of severity indicators (polypnea, SatO2 ≤ 93% and PaO2/FiO2 ≤ 300) and an association with poor outcomes was also found, namely mechanical ventilation requirement and in-hospital/30-day mortality (p < 0.05). Conclusion: Hyperglycemia at admission was associated with poor outcomes in COVID-19 patients, even in those without known pre-existing diabetes. Glycemic testing should be recommended for all COVID-19 patients.

Estradiol Protects Female ApoE KO Mice against Western-Diet-Induced Non-Alcoholic Steatohepatitis.

The prevalence of non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), is higher in men than in women of reproductive age, and postmenopausal women are especially susceptible to developing the disease. AIM: we evaluated if female apolipoprotein E (ApoE) KO mice were protected against Western-diet (WD)-induced NASH. METHODS: Female ovariectomized (OVX) ApoE KO mice or sham-operated (SHAM) mice were fed either a WD or a regular chow (RC) for 7 weeks. Additionally, OVX mice fed a WD were treated with either estradiol (OVX + E2) or vehicle (OVX). RESULTS: Whole-body fat, plasma glucose, and plasma insulin were increased and associated with increased glucose intolerance in OVX mice fed a WD (OVX + WD). Plasma and hepatic triglycerides, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) hepatic enzymes were also increased in the plasma of OVX + WD group, which was associated with hepatic fibrosis and inflammation. Estradiol replacement in OVX mice reduced body weight, body fat, glycemia, and plasma insulin associated with reduced glucose intolerance. Treatment also reduced hepatic triglycerides, ALT, AST, hepatic fibrosis, and inflammation in OVX mice. CONCLUSIONS: These data support the hypothesis that estradiol protects OVX ApoE KO mice from NASH and glucose intolerance.