Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange dysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomized-controlled trial was performed with the primary aim of assessing the safety of DIALIVE in patients with ACLF, with secondary aims of evaluating its clinical effects, device performance and effect on pathophysiologically relevant biomarkers. METHODS: Thirty-two patients with alcohol-related ACLF were included. Patients were treated with DIALIVE for up to 5 days and end points were assessed at Day 10. Safety was assessed in all patients (n = 32). The secondary aims were assessed in a pre-specified subgroup that had at least three treatment sessions with DIALIVE (n = 30). RESULTS: There were no significant differences in 28-day mortality or occurrence of serious adverse events between the groups. Significant reduction in the severity of endotoxemia and improvement in albumin function was observed in the DIALIVE group, which translated into a significant reduction in the CLIF-C (Chronic Liver Failure consortium) organ failure (p = 0.018) and CLIF-C ACLF scores (p = 0.042) at Day 10. Time to resolution of ACLF was significantly faster in DIALIVE group (p = 0.036). Biomarkers of systemic inflammation such as IL-8 (p = 0.006), cell death [cytokeratin-18: M30 (p = 0.005) and M65 (p = 0.029)], endothelial function [asymmetric dimethylarginine (p = 0.002)] and, ligands for Toll-like receptor 4 (p = 0.030) and inflammasome (p = 0.002) improved significantly in the DIALIVE group. CONCLUSIONS: These data indicate that DIALIVE appears to be safe and impacts positively on prognostic scores and pathophysiologically relevant biomarkers in patients with ACLF. Larger, adequately powered studies are warranted to further confirm its safety and efficacy. IMPACT AND IMPLICATIONS: This is the first-in-man clinical trial which tested DIALIVE, a novel liver dialysis device for the treatment of cirrhosis and acute-on-chronic liver failure, a condition associated with severe inflammation, organ failures and a high risk of death. The study met the primary endpoint, confirming the safety of the DIALIVE system. Additionally, DIALIVE reduced inflammation and improved clinical parameters. However, it did not reduce mortality in this small study and further larger clinical trials are required to re-confirm its safety and to evaluate efficacy. CLINICAL TRIAL NUMBER: NCT03065699.

Unwilling or unable? Using three-dimensional tracking to evaluate dogs' reactions to differing human intentions.

The extent to which dogs (Canis familiaris) as a domesticated species understand human intentions is still a matter of debate. The unwilling-unable paradigm has been developed to examine whether nonhuman animals are sensitive to intentions underlying human actions. In this paradigm, subjects tended to wait longer in the testing area when presented with a human that appeared willing but unable to transfer food to them compared to an unwilling (teasing) human. In the present study, we conducted the unwilling-unable paradigm with dogs using a detailed behavioural analysis based on machine-learning driven three-dimensional tracking. Throughout two preregistered experiments, we found evidence, in line with our prediction, that dogs reacted more impatiently to actions signalling unwillingness to transfer food rather than inability. These differences were consistent through two different samples of pet dogs (total n = 96) and they were evident also in the machine-learning generated three-dimensional tracking data. Our results therefore provide robust evidence that dogs distinguish between similar actions (leading to the same outcome) associated with different intentions. However, their reactions did not lead to any measurable preference for one experimenter over the other in a subsequent transfer phase. We discuss different cognitive mechanisms that might underlie dogs' performance in this paradigm.

ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA): a multi-centre prospective cohort study protocol.

BACKGROUND: Emerging evidence points at substantial comorbidity between adult attention deficit hyperactivity disorder (ADHD) and cardiometabolic diseases, but our understanding of the comorbidity and how to manage cardiometabolic disease in adults with ADHD is limited. The ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA) project uses remote measurement technology to obtain real-world data from daily life to assess the extent to which ADHD medication treatment and physical activity, individually and jointly, may influence cardiometabolic risks in adults with ADHD. Our second main aim is to obtain valuable real-world data on adherence to pharmacological treatment and its predictors and correlates during daily life from adults with ADHD. METHODS: ART-CARMA is a multi-site prospective cohort study within the EU-funded collaboration 'TIMESPAN' (Management of chronic cardiometabolic disease and treatment discontinuity in adult ADHD patients) that will recruit 300 adults from adult ADHD waiting lists. The participants will be monitored remotely over a period of 12 months that starts from pre-treatment initiation. Passive monitoring, which involves the participants wearing a wrist-worn device (EmbracePlus) and downloading the RADAR-base Passive App and the Empatica Care App on their smartphone, provides ongoing data collection on a wide range of variables, such as physical activity, sleep, pulse rate (PR) and pulse rate variability (PRV), systolic peaks, electrodermal activity (EDA), oxygen saturation (SpO2), peripheral temperature, smartphone usage including social connectivity, and the environment (e.g. ambient noise, light levels, relative location). By combining data across these variables measured, processes such as physical activity, sleep, autonomic arousal, and indicators of cardiovascular health can be captured. Active remote monitoring involves the participant completing tasks using a smartphone app (such as completing clinical questionnaires or speech tasks), measuring their blood pressure and weight, or using a PC/laptop (cognitive tasks). The ART system is built on the RADAR-base mobile-health platform. DISCUSSION: The long-term goal is to use these data to improve the management of cardiometabolic disease in adults with ADHD, and to improve ADHD medication treatment adherence and the personalisation of treatment.

Laboratory diagnosis of Clostridioides (Clostridium) difficile infection in domestic animals: A short review.

Despite the known importance of Clostridioides (Clostridium) difficile infection (CDI) in animals, there are no published guidelines for the diagnosis of CDI. The performance of the available commercial methods, all standardized for human stool samples, can vary according to the animal species. Thus, the aim of the present study was to review the literature on the detection of C. difficile in pigs, horses, and dogs. The detection of toxins A and B using enzyme immunoassays seems to have low performance in piglet and dog samples, while it shows high sensitivity for the diagnosis of CDI in foals. On the other hand, tests for the detection of glutamate dehydrogenase (GDH) have a high sensitivity towards detection of C. difficile in animal samples, suggesting that it can be an adequate screening method. A few studies have evaluated real-time PCR or nucleic acid amplification tests in animal samples and, so far, these methods have also shown a low performance for the detection of C. difficile in animals. Although the intestinal lesions caused by CDI can vary among animal species, histopathology can be a useful auxiliary tool for postmortem diagnosis in animals.

Childhood Hypophosphatasia Associated with a Novel Biallelic ALPL Variant at the TNSALP Dimer Interface.

The goal of this study was to perform a clinical and molecular investigation in an eight-year-old female child diagnosed with hypophosphatasia (HPP). The proband and her family were evaluated by medical and dental histories, biochemical analyses, radiographic imaging, and genetic analysis of the tissue-nonspecific alkaline phosphatase (ALPL) gene. A bioinformatic analysis was performed to predict the structural and functional impact of the point mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) molecule and to define their potential contribution to the phenotype. We identified a novel combination of heterozygous ALPL missense variants in the proband, p.Ala33Val and p.Asn47His, compatible with an autosomal recessive mode of inheritance and resulting in skeletal and dental phenotypes. Computational modeling showed that the affected Asn47 residue is located in the coil structure close to the N-terminal α-helix, whereas the affected Ala33 residue is localized in the N-terminal α-helix. Both affected residues are located close to the homodimer interface, suggesting they may impair TNSALP dimer formation and stability. Clinical and biochemical follow-up revealed improvements after six years of ERT. Reporting this novel combination of ALPL variants in childhood HPP provides new insights into genotype-phenotype associations for HPP and specific sites within the TNSALP molecule potentially related to a childhood-onset HPP and skeletal and dental manifestations. Beneficial effects of ERT are implicated in skeletal and dental tissues.

Virulence Genes Profile and Antimicrobial Susceptibility of Community-Acquired Bacterial Urinary Tract Infections in a Brazilian Hospital.

Urinary tract infections (UTI) are one of the most common diseases worldwide and Escherichia coli is the most common causative bacteria. Empirical treatment is challenging due to antimicrobial or multidrug-resistance. The aims of this study were to determine the uropathogens and their antimicrobial susceptibility profile, as well as to identify the phylogroups and virulence genes of E. coli strains, associated with community-acquired UTI in outpatients admitted at a Brazilian Hospital in southeast Brazil. In total, 47 bacterial strains were isolated from 47 patients, 44 women and 2 men (no gender record from one patient). The age of the patients whose urine culture were positive varied from 0 (less than one month) to 104 years. Most of the isolates were E. coli (41/47), followed by Klebsiella pneumoniae (2/47), Klebsiella variicola/Klebsiella aerogenes (1/47), Pseudomonas aeruginosa (1/47), Proteus mirabilis (1/47), and Citrobacter koseri (1/47). Most E. coli strains were classified as phylogroup B2 (15/41 = 36.59%) and B1 (12/41 = 29.27%) and the most common virulence genes among E. coli strains were fimH (31/41 = 75.61%), iutA (21/41 = 51.22%), and tratT (16/41 = 39.02%). Among the E. coli strains, 59% were multidrug-resistance and strains that were ampicillin, sulfamethoxazole/trimethoprim, or tetracycline-resistant exhibited more chance to be multidrug-resistance, with an odds ratio of 100.00 [95% confidence interval (CI) 9.44-1059.26], 22.50 (95% CI 3.95-128.30), and 12.83 (95% CI 2.68-61.45), respectively. Our results showed that E. coli was the main etiological agent identified and demonstrated high frequency of multidrug-resistance and virulence factors in bacterial strains isolated from UTIs.

Outcomes of Patients with Central Precocious Puberty Due to Loss-of-Function Mutations in the MKRN3 Gene after Treatment with Gonadotropin-Releasing Hormone Analog.

INTRODUCTION: Loss-of-function mutation of MKRN3 represents the most frequent genetic cause of familial central precocious puberty (CPP). The outcomes of gonadotropin-releasing hormone analog (GnRHa) treatment in CPP patients with MKRN3 defects are unknown. OBJECTIVE: To describe the clinical and hormonal features of patients with CPP with or without MKRN3 mutations after GnRHa treatment. Anthropometric, metabolic and reproductive parameters were evaluated. PATIENTS AND METHODS: Twenty-nine female patients with CPP due to loss-of-function mutations in the MKRN3 and 43 female patients with idiopathic CPP were included. Their medical records were retrospectively evaluated for clinical, laboratory, and imaging study, before, during, and after GnRHa treatment. All patients with idiopathic CPP and 11 patients with CPP due to MKRN3 defects reached final height (FH). RESULTS: At the diagnosis, there were no significant differences between clinical and laboratory features of patients with CPP with or without MKRN3 mutations. A high prevalence of overweight and obesity was observed in patients with CPP with or without MKRN3 mutations (47.3 and 50%, respectively), followed by a significant reduction after GnRHa treatment. No significant differences in the values of mean FH and target height were found between the 2 CPP groups after GnRHa treatment. Menarche occurred at the expected age in patients with or without CPP due to MKRN3 mutations (11.5 ± 1.3 and 12 ± 0.6 years, respectively). The prevalence of polycystic ovarian syndrome was 9.1% in patients with CPP due to MKRN3 mutations and 5.9% in those with idiopathic CPP. CONCLUSION: Anthropometric, metabolic, and reproductive outcomes after GnRHa treatment were comparable in CPP patients, with or without MKRN3 mutations, suggesting the absence of deleterious effects of MKRN3 defects in young female adults' life.

Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV).

OBJECTIVE: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. DESIGN: International, multicenter, prospective, randomized controlled clinical trial. SETTING: A network of university hospitals. PARTICIPANTS: The study comprises 1,380 patients scheduled for thoracic surgery. INTERVENTIONS: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. MEASUREMENTS AND MAIN RESULTS: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients.

The interplay between ambient temperature and salt intake affects oxidative status and immune responses in a ubiquitous Neotropical passerine, the rufous-collared sparrow.

Physiological traits associated with maintenance, growth, and reproduction demand a large amount of energy and thus directly influence an animal's energy budget, which is also regulated by environmental conditions. In this study, we evaluated the interplay between ambient temperature and salinity of drinking water on energy budgets and physiological responses in adult Rufous-collared sparrow (Zonotrichia capensis), an omnivorous passerine that is ubiquitous in Chile and inhabits a wide range of environments. We acclimated birds to 30 days at two ambient temperatures (27 °C and 17 °C) and drinking water salinity (200 mM NaCl and fresh water) conditions. We evaluated: 1) the aerobic scope and the activities of mitochondrial metabolic enzymes, 2) osmoregulatory parameters, 3) the skin-swelling immune response to an antigen, 4) oxidative status, and 5) the length of telomeres of red blood cells. Our results confirm that Z. capensis tolerates the chronic consumption of moderate levels of salt, maintaining body mass but increasing their basal metabolic rates consistent with expected osmoregulatory costs. Additionally, the factorial aerobic scope was higher in birds acclimated to fresh (tap) water at both 17° and 27 °C. Drinking water salinity and low ambient temperatures negatively impacted inflammatory response, and we observed an increase in lipid peroxidation and high levels of circulating antioxidants at low temperatures. Finally, telomere length was not affected by osmo- and thermoregulatory stress. Our results did not support the existence of an interplay between environmental temperature and drinking water salinity on most physiological and biochemical traits in Z. capensis, but the negative effect of these two factors on the inflammatory immune response suggests the existence of an energetic trade-off between biological functions that act in parallel to control immune function.

Long-Term Outcomes of Patients with Central Precocious Puberty due to Hypothalamic Hamartoma after GnRHa Treatment: Anthropometric, Metabolic, and Reproductive Aspects.

BACKGROUND: Hypothalamic hamartoma (HH) represents the commonest cause of organic central precocious puberty (CPP). Follow-up of these patients in adulthood is scarce. OBJECTIVE: To describe the anthropometric, metabolic, and reproductive parameters of patients with CPP due to HH before and after treatment with gonadotropin-releasing hormone analog (GnRHa). METHODS: We performed a retrospective and cross-sectional study in a single tertiary center including 14 patients (7 females) with CPP due to HH. RESULTS: The mean duration of GnRHa treatment was 7.7 ± 2.4 years in boys and 7.9 ± 2.1 years in girls. GnRHa treatment was interrupted at the mean chronological age (CA) of 12.1 ± 1.1 years in boys and 10.7 ± 0.5 years in girls. At the last visit, the mean CA of the male and female patients was 21.5 ± 3.2 and 24 ± 3.9 years, respectively. Eleven of the 14 patients reached normal final height (FH) (standard deviation score -0.6 ± 0.9 for males and -0.6 ± 0.5 for females), all of them within the target height (TH) range. The remaining 3 patients had predicted height within the TH range. The mean body mass index and the percentage of body fat mass was significantly higher in females, with a higher prevalence of metabolic disorders. All patients presented normal gonadal function in adulthood, and 3 males fathered a child. CONCLUSION: All patients with CPP due to HH reached normal FH or near-FH. A higher prevalence of overweight/obesity and hypercholesterolemia was observed in the female patients. Finally, no reproductive disorder was identified in both sexes, indicating that HH per se has no deleterious effect on the gonadotropic axis in adulthood.

Anodal transcranial direct current stimulation over the posterior parietal cortex reduces the onset time to the rubber hand illusion and increases the body ownership.

The body ownership induced by the rubber hand illusion (RHI) has been related to a neural network involving a frontal-parietal circuit. Previous functional neuroimaging studies have demonstrated neural activation in the parietal area relative to the multisensory integration processing and to the recalibration of the felt position of body while a ventral premotor cortex activation has been linked to bodily self-attribution during the RHI. Our study aimed to investigate the effects of transcranial direct current stimulation (tDCS) on the posterior parietal cortex (PPC) or on the premotor cortex (PMv) during RHI to address the specific roles of these two brain areas in the illusion. 156 young adult participants (21.2 ± 3.13 years old; all right-handed) were enrolled for this between-subjects design experiment. Participants received anodal, cathodal and sham tDCS in three different sessions on the right PPC or right PMv and experienced visual-tactile stimulation from the brushes touching the rubber hand and their own left hand in synchronous or asynchronous manner. The RHI was quantified by the (1) onset time for the feeling of body ownership of the rubber hand, (2) proprioceptive drift, and (3) questionnaire about the intensity of the illusion as reported by the participant. All subjects felt the RHI during the synchronous condition. However, we found that the illusion onset time can be modulated by the anodal tDCS condition on the PPC: anodal tDCS decreased the illusion onset time and the subjective experience of body ownership. These findings suggest that the parietal area plays a crucial role in the speed of visual and tactile multisensory integration in the RHI and introduce tDCS as technique that can accelerate the time to integrate an artificial body part and increased the perception of body ownership.

Isolation of Candida auris from 9 patients in Central America: Importance of accurate diagnosis and susceptibility testing.

Candida auris is an emerging multidrug-resistant (MDR) fungus associated with invasive infections and high mortality. This report describes 9 patients from whom C. auris was isolated at a hospital in Panama City, Panama, the first such cases in Central America, and highlights the challenges of accurate identification and methods for susceptibility testing.

Influence of Chronic Alcohol Use on Osteoblastic Differentiation of Bone Marrow Cells, Bone Properties, and Hepatic and Renal Morphology of Rats.

Chronic alcohol exposure can affect the osteoblastic activity and the proliferation and differentiation of cells due to its toxic effect, which can affect negatively bone repair and bone microarchitecture. The aim of this study was to evaluate the effects of chronic use of 20% alcohol on rats regarding osteoblastic differentiation, extrinsic and intrinsic properties of the tibia, and hepatic and renal morphology. Wistar rats were divided into three groups (n = 9) in accordance with a 24-week diet. After euthanasia, kidneys, liver, and tibias were removed for analysis and femurs mesenchymal cells were collected. The results showed that chronic use of 20% alcohol influenced neither the alkaline phosphatase production nor total protein (p > 0.05) in rats, with similar formation of nodules in all groups (p > 0.05). However, significant changes in the liver and kidneys and adverse effects on the mechanical properties of the tibia were observed. According to the results, it can be concluded that the chronic use of alcohol for 24 weeks had no negative influence on the activity and differentiation of osteoblasts, but the mechanical properties of the tibia were impaired and the organs responsible for metabolism and excretion were also affected due to the consumption of alcohol.

CaP Coating and Low-Level Laser Therapy to Stimulate Early Bone Formation and Improve Fixation of Rough Threaded Implants.

PURPOSE: This study aimed to compare in vivo osteogenesis on rough threaded dental implants with and without calcium phosphate (CaP) coating deposition, alone or in association with low-level laser therapy (LLLT) by gallium aluminum arsenide. MATERIAL AND METHODS: Four groups were studied: G1: implant; G2: implant + CaP coating; G3: implant + LLLT; and G4: implant + CaP coating + LLLT. LLLT was applied for 7 days at the surgical site before and after placing the implant. Topographic characterization was performed before surgery using scanning electron microscopy and energy dispersion spectrophotometry. Bone-implant contact (BIC) was measured after 1, 2, and 6 weeks and reverse torque after 6 weeks. In short periods, G2, G3, and G4 showed significantly greater BIC than G1 (P < 0.05), but no difference in BIC was observed at 6 weeks. However, the values for the removal torque test at 6 weeks were higher in G2 and G4 (P < 0.05). CONCLUSION: Both CaP coating alone and using LLLT induce cellular stimulation and improve BIC in short-term healing, resulting in higher implant fixation, and should be considered in clinical practice due to their low cost and high effectiveness.

Natural History of Conversion of Leber's Hereditary Optic Neuropathy: A Prospective Case Series.

PURPOSE: To illustrate the natural history of Leber's hereditary optic neuropathy (LHON). DESIGN: Prospective observational case series. PARTICIPANTS: The Soave-Brazil pedigree of m.11778G>A/ND4 mitochondrial DNA LHON mutation. METHODS: A prospectively acquired database of the Soave-Brazil pedigree was reviewed. Data from 285 individuals were included in the database over a 15-year period. The pedigree was reviewed for unaffected mutation carriers who converted to affected status, 6 patients with LHON were identified. The medical records were reviewed 1 year preconversion to 1 year postconversion for visual acuity (logarithm of the minimum angle of resolution [logMAR]), Humphrey Visual Field (HVF) mean deviation (MD), and retinal nerve fiber layer (RNFL) thickness, as measured by Cirrus (Carl Zeiss, Oberkochen, Germany) optic coherence tomography (OCT). The RNFL thickness values were normalized for age. Visual acuity, HVF, and processed RNFL data from each of the 12 eyes were then sorted into 2-month time periods relative to the date of conversion, within which they were averaged. MAIN OUTCOME MEASURES: The main outcome measures were visual acuity, HVF MD, and RNFL thickness. RESULTS: Decreased visual acuity preceded conversion by up to 2 months and then declined up to 8 months postconversion. Decrease in HVF MD occurred at least 4 months preceding conversion, after which values decreased until plateau at 6 to 8 months. Average RNFL thickness was above normal baseline thickness in all 4 quadrants as measured by OCT at the time of conversion. Increase in RNFL thickness preceded conversion as early as 4 to 6 months, peaked at conversion, and decreased until individual plateaus. The temporal quadrant was first to be involved, then the inferior and superior quadrants, and the nasal quadrant showed the latest and least changes. CONCLUSIONS: Subclinical changes preceded the date of conversion and may reflect the complicated nature of identifying the date of conversion in LHON. Early increases in RNFL preceding conversion suggest that structural changes precede clinically significant vision loss. Asynchronous quadrant involvement supports a previously published mathematical model. The natural history of LHON is not a subacute process, as previously believed, but progresses more slowly, taking up to 8 months to plateau.

[Loss of pubescence and their physiological effects on endangered rosette Espeletia paipana (Asteraceae), Boyacá-Colombia]. / Pérdida de pubescencia foliar y sus efectos fisiológicos en la roseta en peligro de extinción Espeletia paipana (Asteraceae), en Boyacá-Colombia.

Espeletia paipana is an endangered giant caulescent rosette endemic to (Asteraceae), Boyacdi-Colombia. Espelelia paipana is an endangered giant caulescent rosette endemic to Boyacá department. In order to establish whether a plant disease, characterized by the loss of leaf pubescence (PPF) and attributed to the pathogenic action of endophytic microorganisms, is the cause of the increasing mortality of population, the physiological performance of the species was evaluated with and without PPF. The incidence (% leaves affected in each of the 27 individuals in the current population) and severity (% leaf area affected on 135 leaves) of the PPF were monitored over a period of nine months, in three topographic zones of different heights. During four consecutive days in both dry and wet season, physiological parameters as chlorophyll content index (ICC), stomatal conductance (Gs) and leaf temperature (Tfol) were measured in healthy and affected leaves. The study was complemented with isolations and pathogenicity tests to identify the causal agent of the PPF. Overall, although the disease incidence in E. paipana was constant over time, the severity progressed surpassing 60 % of the leaf area. The increasing of severity in the upper side of leaves was attributed to the photo-oxidative effect of high radiation between 11:00 h and 14:00 h of the day. The reduction of functional leaf area because of the PPF, led to low Gs with serious implications for carbon fixation and thus limiting growth and biomass renewal. The effect of season in Tfol varied according to the topographic zone, while the ICC did not present a defined pattern with respect to the PPF; its low values could be associated with the production of other pigments. Finally, although it is not possible to ensure that Botrytis sp. is the causative of the loss of leaf pubescence, it is postulated as the most probably causal agent due to its high representativeness in the isolates and its infectious potential during the pathogenicity tests. In general, the reduction of healthy leaf biomass and decrease of physiological performance suggest that PPF affect negatively the survival of E. paipana, which means that the use of biological controllers could be a strategy to mitigate its effect on the population.

Effect of incorporation of remineralizing agents into bleaching gels on the microhardness of bovine enamel in situ.

AIM: This study evaluated the effect of adding calcium or fluoride to 35% hydrogen peroxide (HP) bleaching gel and the effect of human saliva on the microhardness of sound and demineralized enamel, using an in situ model. MATERIALS AND METHODS: Cylindrical bovine enamel specimens (3 × 2 mm) were divided into two groups (n = 30): sound enamel (SE) and demineralized enamel (DE). Each group was divided into three subgroups, according to the bleaching gel: 35% HP; 35% HP + calcium; 35% HP + fluoride. After bleaching therapy, the specimens were fixed to intraoral devices worn by 10 volunteers for 7 days. Surface enamel microhardness (SMH) was measured before and after bleaching procedures, and after 1 and 7 days of saliva exposure. Data were analyzed by Repeated Measures ANOVA (5%). RESULTS: The variable time resulted in significant differences for SE and DE groups (p = 0.001). For SE, significantly lower SMH was detected for control at post-bleaching period in comparison to the baseline and after 7 days. For DE, the lowest mean values were obtained before bleaching, and the addition of calcium to the peroxide significantly increased enamel SMH. The exposure to human saliva resulted in increased SMH. CONCLUSION: The addition of potential remineralizing agents into bleaching gels might play an important role in maintaining the microhardness of sound enamel and in inducing remineralization of artificially demineralized enamel right after bleaching, and the remineralizing action of human saliva might minimize the deleterious effects of bleaching gels on enamel. Clinical significance: The incorporation of calcium into HP bleaching gel might be beneficial for the initial phases of the bleaching procedure.

Taxon-dependent diversity response along a temperate elevation gradient covered by grassland.

Elevational gradients constitute excellent systems for understanding the mechanisms that generate and maintain global biodiversity patterns. Climatic gradients associated with elevation show strong influence on species distribution in mountains. The study of mountains covered by the same habitat type is an ideal scenario to compare alternatives to the energy hypotheses. Our aim was to investigate how changes in climatic conditions along the elevational gradient drive α- and ß-diversity of four taxa in a mountain system located within a grassland biome. We sampled ants, spiders, birds and plants, and measured climatic variables at six elevational bands (with 10 sampling sites each) established between 470 and 1,000 masl on a mountain from the Ventania Mountain System, Argentina. Species richness per site and ß-diversity (turnover and nestedness) between the lowest band and upper sites were estimated. For most taxa, species richness declined at high elevations and energy, through temperature, was the major driver of species richness for ants, plants and birds, prevailing over productivity and water availability. The major ß-diversity component was turnover for plants, spiders and birds, and nestedness for ants. The unique environmental conditions of the upper bands could favour the occurrence of specialist and endemic species.

Characterization of the plasma proteome from healthy adult dogs.

Introduction: Bloodwork is a widely used diagnostic tool in veterinary medicine, as diagnosis and therapeutic interventions often rely on blood biomarkers. However, biomarkers available in veterinary medicine often lack sensitivity or specificity. Mass spectrometry-based proteomics technology has been extensively used in the analysis of biological fluids. It offers excellent potential for a more comprehensive characterization of the plasma proteome in veterinary medicine. Methods: In this study, we aimed to identify and quantify plasma proteins in a cohort of healthy dogs and compare two techniques for depleting high-abundance plasma proteins to enable the detection of lower-abundance proteins via label-free quantification liquid chromatography-mass spectrometry. We utilized surplus lithium-heparin plasma from 30 healthy dogs, subdivided into five groups of pooled plasma from 6 randomly selected individuals each. Firstly, we used a commercial kit to deplete high-abundance plasma proteins. Secondly, we employed an in-house method to remove albumin using Blue-Sepharose. Results and discussion: Among all the samples, some of the most abundant proteins identified were apolipoprotein A and B, albumin, alpha-2-macroglobulin, fibrinogen beta chain, fibronectin, complement C3, serotransferrin, and coagulation factor V. However, neither of the depletion techniques achieved significant depletion of highly abundant proteins. Despite this limitation, we could detect and quantify many clinically relevant proteins. Determining the healthy canine proteome is a crucial first step in establishing a reference proteome for canine plasma. After enrichment, this reference proteome can later be utilized to identify protein markers associated with different diseases, thereby contributing to the diagnosis and prognosis of various pathologies.

Bioprospecting of Artemisia genus: from artemisinin to other potentially bioactive compounds.

Species from genus Artemisia are widely distributed throughout temperate regions of the northern hemisphere and many cultures have a long-standing traditional use of these plants as herbal remedies, liquors, cosmetics, spices, etc. Nowadays, the discovery of new plant-derived products to be used as food supplements or drugs has been pushed by the exploitation of bioprospection approaches. Often driven by the knowledge derived from the ethnobotanical use of plants, bioprospection explores the existing biodiversity through integration of modern omics techniques with targeted bioactivity assays. In this work we set up a bioprospection plan to investigate the phytochemical diversity and the potential bioactivity of five Artemisia species with recognized ethnobotanical tradition (A. absinthium, A. alba, A. annua, A. verlotiorum and A. vulgaris), growing wild in the natural areas of the Verona province. We characterized the specialized metabolomes of the species (including sesquiterpenoids from the artemisinin biosynthesis pathway) through an LC-MS based untargeted approach and, in order to identify potential bioactive metabolites, we correlated their composition with the in vitro antioxidant activity. We propose as potential bioactive compounds several isomers of caffeoyl and feruloyl quinic acid esters (e.g. dicaffeoylquinic acids, feruloylquinic acids and caffeoylferuloylquinic acids), which strongly characterize the most antioxidant species A. verlotiorum and A. annua. Morevoer, in this study we report for the first time the occurrence of sesquiterpenoids from the artemisinin biosynthesis pathway in the species A. alba.