Monitoring emerging pathogens using negative nucleic acid test results from endemic pathogens in pig populations: Application to porcine enteric coronaviruses.

This study evaluated the use of endemic enteric coronaviruses polymerase chain reaction (PCR)-negative testing results as an alternative approach to detect the emergence of animal health threats with similar clinical diseases presentation. This retrospective study, conducted in the United States, used PCR-negative testing results from porcine samples tested at six veterinary diagnostic laboratories. As a proof of concept, the database was first searched for transmissible gastroenteritis virus (TGEV) negative submissions between January 1st, 2010, through April 29th, 2013, when the first porcine epidemic diarrhea virus (PEDV) case was diagnosed. Secondly, TGEV- and PEDV-negative submissions were used to detect the porcine delta coronavirus (PDCoV) emergence in 2014. Lastly, encountered best detection algorithms were implemented to prospectively monitor the 2023 enteric coronavirus-negative submissions. Time series (weekly TGEV-negative counts) and Seasonal Autoregressive-Integrated Moving-Average (SARIMA) were used to control for outliers, trends, and seasonality. The SARIMA's fitted and residuals were then subjected to anomaly detection algorithms (EARS, EWMA, CUSUM, Farrington) to identify alarms, defined as weeks of higher TGEV-negativity than what was predicted by models preceding the PEDV emergence. The best-performing detection algorithms had the lowest false alarms (number of alarms detected during the baseline) and highest time to detect (number of weeks between the first alarm and PEDV emergence). The best-performing detection algorithms were CUSUM, EWMA, and Farrington flexible using SARIMA fitted values, having a lower false alarm rate and identified alarms 4 to 17 weeks before PEDV and PDCoV emergences. No alarms were identified in the 2023 enteric negative testing results. The negative-based monitoring system functioned in the case of PEDV propagating epidemic and in the presence of a concurrent propagating epidemic with the PDCoV emergence. It demonstrated its applicability as an additional tool for diagnostic data monitoring of emergent pathogens having similar clinical disease as the monitored endemic pathogens.

Localized K63 ubiquitin signaling is regulated by VCP/p97 during oxidative stress.

Under stress conditions, cells reprogram their molecular machineries to mitigate damage and promote survival. Ubiquitin signaling is globally increased during oxidative stress, controlling protein fate and supporting stress defenses at several subcellular compartments. However, the rules driving subcellular ubiquitin localization to promote these concerted response mechanisms remain understudied. Here, we show that K63-linked ubiquitin chains, known to promote proteasome-independent pathways, accumulate primarily in non-cytosolic compartments during oxidative stress induced by sodium arsenite in mammalian cells. Our subcellular ubiquitin proteomic analyses of non-cytosolic compartments expanded 10-fold the pool of proteins known to be ubiquitinated during arsenite stress (2,046) and revealed their involvement in pathways related to immune signaling and translation control. Moreover, subcellular proteome analyses revealed proteins that are recruited to non-cytosolic compartments under stress, including a significant enrichment of helper ubiquitin-binding adaptors of the ATPase VCP that processes ubiquitinated substrates for downstream signaling. We further show that VCP recruitment to non-cytosolic compartments under arsenite stress occurs in a ubiquitin-dependent manner mediated by its adaptor NPLOC4. Additionally, we show that VCP and NPLOC4 activities are critical to sustain low levels of non-cytosolic K63-linked ubiquitin chains, supporting a cyclical model of ubiquitin conjugation and removal that is disrupted by cellular exposure to reactive oxygen species. This work deepens our understanding of the role of localized ubiquitin and VCP signaling in the basic mechanisms of stress response and highlights new pathways and molecular players that are essential to reshape the composition and function of the human subcellular proteome under dynamic environments.

Influence of bovine pestivirus heterogeneity on serological responses to 10 different commercial vaccine formulation.

Bovine Pestivirus typically involves one or more organ systems, with clinical manifestations ranging from mild to severe fatal systemic illness that lead to significant reproductive, productive, and economic losses. Vaccines face the challenge of addressing the significant variability of pestiviruses, which affects the interaction between viral antigens and the immune system's ability to provide protection. This study aimed to evaluate the serological responses against bovine viral diarrhea virus 1 (Pestivirus A) and Pestivirus B induced by 10 commercial vaccines, including one recombinant (vaccine E), two modified live (MLV multivalent, vaccine I, and MLV monovalent, vaccine J), and seven killed vaccines (KLV, vaccines A to H). Additionally, we evaluated the cross-reactivity between Pestivirus A and B from vaccines and HoBi-like pestivirus (Pestivirus H). In Phase 1, guinea pigs were used to screen for non-MLVs. They were divided into nine groups (n=6 each) and received two doses (⅕ of bovine dose) of eight different non-MLV on Days 0 and 21. Serum samples were collected on Days 0 and 30 for serological analyse. In Phase 2, Holstein × Gir heifers (n= 45) were divided into five groups, comprising 6-9 animals. They were vaccinated either once with MLVs or twice with the top non-MLVs screened in Phase 1. Serum samples were harvested on d0 (vaccination day) and d60 (60 days after the first dose) for MLV and non-MLV. Specific antibody titers were assessed virus neutralization (VN) and transformed in log2 for statistical analysis using PROC-MIXED. Significant effects were observed for vaccine groups, time points, and their interactions concerning neutralizing antibodies against Pestivirus A and B in both Guinea pigs and heifers. The Phase 1 study revealed serological responses against Pestivirus A exclusively in non-MLV D (85.33±13.49) and E (72.00±19.26). In the bovine study, the KLD vaccine D (72.00±15.10), recombinant vaccine E (90.66±25.85), and MLV I (170.66±28.22) resulted in an average of neutralizing antibodies against Pestivirus A that exceeded the protective threshold (≥ 60). However,individual analysis of heifers showed a higher frequency of animals presenting titers of Pestivirus A Ab surpassing 32 following vaccination with MLV I and J. None of the vaccine formulations in either study elicited a protective immune response against Pestivirus B or demonstrated cross-reactivity against Pestivirus H.

Control of Anisotropy and Magnetic Hyperthermia Effect by Addition of Cobalt on Magnetite Nanoparticles.

Magnetic hyperthermia (MH) has emerged as a promising technology with diverse applications in medical and technological fields, leveraging the remote induction of temperature elevation through an alternating magnetic field. While Fe3O4 nanoparticles with an average size around 12-25 nm are commonly employed in MH systems, this study introduces a strategy to produce smaller particles (less than or equal to 10 nm) with enhanced heating efficiency, as measured by specific power absorption (SPA). We conducted an exhaustive and detailed investigation into the morphological and magnetic properties of CoxFe3-xO4 nanoparticles, aiming to optimize their MH response. By varying the Co content, we successfully tuned the effective magnetic anisotropy while maintaining saturation magnetization nearly constant. The MH analysis indicates that these nanoparticles predominantly heat through the Néel mechanism, demonstrating robust reproducibility across different concentrations, viscosity mediums, and ac field conditions. Notably, we identified an optimal anisotropy or Co concentration that maximizes SPA, crucial for developing magnetic systems requiring particles with specific sizes. This work contributes to advancing the understanding and application of MH, particularly in tailoring nanoparticle properties for targeted and efficient heat generation in various contexts.

Blended e-learning and certification for medicines development professionals: results of a 7-year collaboration between King's College, London and the GMDP Academy, New York.

Introduction: The field of Medicines Development faces a continuous need for educational evolution to match the interdisciplinary and global nature of the pharmaceutical industry. This paper discusses the outcomes of a 7-year collaboration between King's College London and the Global Medicines Development Professionals (GMDP) Academy, which aimed to address this need through a blended e-learning program. Methods: The collaboration developed a comprehensive curriculum based on the PharmaTrain syllabus, delivered through a combination of asynchronous and synchronous e-learning methods. The program targeted a diverse range of professionals serving in areas related to Medical Affairs. Results: Over seven annual cohorts, 682 participants from eighty-six countries were enrolled in the program. The program's effectiveness was assessed using Kirkpatrick's model, showing elevated levels of satisfaction (over 4.0 on a five-point scale), suggesting significant gains in competence at the cognitive level and leveraged performance. Notably, 70% of responding alumni reported significant improvement in their functions, corroborated by 30% of their supervisors. The further long-term impact of the program on their respective organization has not been established. Discussion: The GMDP Academy's program has significantly contributed to life-long learning in Medicines Development, addressing educational gaps and fostering interdisciplinary collaboration. Its success highlights the importance of continuous education in keeping pace with the industry's evolving demands and underscores the potential of blended learning in achieving educational objectives in pharmaceutical medicine.

Trans-cyclooctene-a Swiss army knife for bioorthogonal chemistry: exploring the synthesis, reactivity, and applications in biomedical breakthroughs.

BACKGROUND: Trans-cyclooctenes (TCOs) are highly strained alkenes with remarkable reactivity towards tetrazines (Tzs) in inverse electron-demand Diels-Alder reactions. Since their discovery as bioorthogonal reaction partners, novel TCO derivatives have been developed to improve their reactivity, stability, and hydrophilicity, thus expanding their utility in diverse applications. MAIN BODY: TCOs have garnered significant interest for their applications in biomedical settings. In chemical biology, TCOs serve as tools for bioconjugation, enabling the precise labeling and manipulation of biomolecules. Moreover, their role in nuclear medicine is substantial, with TCOs employed in the radiolabeling of peptides and other biomolecules. This has led to their utilization in pretargeted nuclear imaging and therapy, where they function as both bioorthogonal tags and radiotracers, facilitating targeted disease diagnosis and treatment. Beyond these applications, TCOs have been used in targeted cancer therapy through a "click-to-release" approach, in which they act as key components to selectively deliver therapeutic agents to cancer cells, thereby enhancing treatment efficacy while minimizing off-target effects. However, the search for a suitable TCO scaffold with an appropriate balance between stability and reactivity remains a challenge. CONCLUSIONS: This review paper provides a comprehensive overview of the current state of knowledge regarding the synthesis of TCOs, and its challenges, and their development throughout the years. We describe their wide ranging applications as radiolabeled prosthetic groups for radiolabeling, as bioorthogonal tags for pretargeted imaging and therapy, and targeted drug delivery, with the aim of showcasing the versatility and potential of TCOs as valuable tools in advancing biomedical research and applications.

Serological Responses of Guinea Pigs and Heifers to Eight Different BoAHV-1 Vaccine Formulations.

Bovine alphaherpesvirus 1 (BoAHV-1) infection affects the production and reproductive performance of dairy and beef livestock, resulting in considerable economic losses. In addition to biosecurity measures, vaccination programs are effective strategies for controlling and preventing BoAHV-1 infection and transmission. We evaluated the serological immune response against BoAHV-1 induced by eight different formulations of commercial vaccines: three modified live vaccines and five killed vaccines containing BoAHV type 1 or types 1 and 5. In the first experiment, 50 BoAHV-1-seronegative guinea pigs were assigned to eight groups; each individual in the treatment groups received two doses (one-fifth of the bovine dose). The second experiment was conducted using 29 crossbred Holstein × Gir heifers in four groups of six to nine animals each. The serological immune response against BoAHV-1 was measured using virus neutralization and enzyme-linked immunosorbent assays to measure the total IgG against BoAHV. We evaluated the effects of the vaccine, time, and interaction of the vaccine and time on neutralizing antibodies against BoAHV-1. Killed vaccines produced low levels of antibodies against BoAHV-1, whereas modified live vaccines produced high levels of antibodies capable of providing neutralizing titers in the vaccinated animals, with the thermosensitive modified live vaccine showing the highest levels of antibodies.

Acute Effects of Breaking up Sitting Time With Isometric Wall Squat Exercise on Vascular Function and Blood Pressure in Sedentary Adults: Randomized Crossover Trial.

PURPOSE: The World Health Organization has recommended breaking up sitting time to improve cardiovascular health. However, whether isometric exercise can be effectively used as a strategy to break up sitting time remains unclear. Thus, the aim of this study was to analyze the acute effects of breaking up prolonged sitting with isometric wall squat exercise (IWSE) on vascular function and blood pressure (BP) in sedentary adults. METHODS: This randomized crossover trial included 17 adults (53% male, 26 ± 6 yr, 22.4 ± 3.6 kg/m2) with high sedentary behavior (≥ 6 hr/d). The participants completed 2 experimental sessions in a randomized order, both sharing a common sitting period of 180 min: Breaks (2-min breaks were incorporated into the IWSE, with participants maintaining their knees at the angle determined by the incremental test, which occurred every 30 min) and Control (sitting for 180 min continuously). Popliteal artery flow-mediated dilation (FMD) and brachial BP were measured before and at 10 and 30 min after the experimental sessions. RESULTS: The results did not indicate significant session vs time interaction effects on popliteal FMD and brachial BP (P > .05). A subanalysis including only participants with popliteal FMD reduction after the Control session (n = 11) revealed that Breaks enhanced popliteal FMD after 10 min (1.38 ± 6.45% vs -4.87 ± 2.95%, P= .002) and 30 min (-0.43 ± 2.48% vs -2.11 ± 5.22%, P= .047). CONCLUSION: Breaking up prolonged sitting with IWSE mitigates impaired vascular function resulting from prolonged sitting but has no effect on BP in sedentary adults.

Validation and optimization of the loop-mediated isothermal amplification (LAMP) technique for rapid detection of wheat stripe mosaic virus, a wheat-infecting pathogen.

BACKGROUND: Wheat stripe mosaic virus (WhSMV) is a significant wheat pathogen that causes substantial yield losses in Brazil and other countries. Although several detection methods are available, reliable and efficient tools for on-site WhSMV detection are currently lacking. In this study, a Loop-Mediated Isothermal Amplification (LAMP) method was developed for rapid and reliable field detection of WhSMV. We designed WhSMV-specific primers for the LAMP assay and optimized reaction conditions for increased sensitivity and specificity using infected plant samples. RESULTS: We have developed a diagnostic method utilizing the Loop-Mediated Isothermal Amplification (LAMP) technique capable of rapidly and reliably detecting WhSMV. The LAMP assay has been optimized to enhance sensitivity, specificity, and cost-effectiveness. CONCLUSION: The LAMP assay described here represents a valuable tool for early WhSMV detection, serving to mitigate the adverse economic and social impacts of this viral pathogen. By enabling swift and accurate identification, this assay can significantly improve the sustainability of cereal production systems, safeguarding crop yields against the detrimental effects of WhSMV.

Roasted yerba mate (Ilex paraguariensis) infusions in bovine milk model before and after in vitro digestion: Bioaccessibility of phenolic compounds, antioxidant activity, protein-polyphenol interactions and bioactive peptides.

Yerba mate is increasingly acknowledged for its bioactive properties and is currently being incorporated into various food and pharmaceutical products. When roasted, yerba mate transforms into mate tea, consumed as a hot aqueous infusion, and has gained popularity. This study investigated the bioaccessibility of phenolic compounds, protein-polyphenol interactions, antioxidant activity, and bioactive peptides in roasted yerba mate infusions, utilizing whole, semi-skimmed, and skimmed bovine milk models. The phytochemical profile of roasted yerba mate was analyzed in infusions with water and milk (whole, semi-skimmed, and skimmed), before and after in vitro digestion, identifying 18 compounds that exhibited variations in composition and presence among the samples. Bioavailability varied across different milk matrices, with milk being four times more efficient as a solvent for extraction. Gastric digestion significantly impacted (p < 0.05) the release of phenolic compounds, such as chlorogenic acid and rutin, with only chlorogenic acid remaining 100 % bioavailable in the infusion prepared with skimmed milk. Protein-polyphenol interaction did not influence protein digestion in different infusions, as there was a similarity in the hydrolysis pattern during the digestive process. Changes in antioxidant activity during digestion phases, especially after intestinal digestion in milk infusions, were related to alterations in protein structures and digestive interactions. The evaluation of total phenolic compounds highlighted that skimmed milk infusion notably preserved these compounds during digestion. Peptidomic analysis identified 253, 221, and 191 potentially bioactive peptides for whole, semi-skimmed, and skimmed milk-digested infusions, respectively, with a focus on anti-inflammatory and anticancer activities, presenting a synergistic approach to promote health benefits. The selection of milk type is crucial for comprehending the effects of digestion and interactions in bioactive compound-rich foods, highlighting the advantages of consuming plant infusions prepared with milk.

The influence of light intensities and micropollutants on the removal of total coliforms and E. coli from wastewater in a flat-panel photobioreactor.

The presence of micropollutants and pathogens in sanitary wastewater and surface water is a growing concern that impacts public health, environmental balance and the maintenance of water supply services. To improve sanitary wastewater treatment, it is necessary to develop and improve sustainable technologies. Among the available options, microalgae-based systems stand out for their efficiency and generation of value-added byproducts. To study the impact of luminosity and the presence of micropollutants (13 selected) on the removal of E. coli and total coliforms from real anaerobically treated wastewater, a pilot flat-panel photobioreactor (50 L) was operated in batch mode in a tropical climate region. This is the first study to evaluate whether micropollutants interfere with coliform groups, considering a microalgae-based system and an experiment in a tropical climate region. E. coli had better removal (from 104 to 101 CFU 100 mL-1) than did total coliforms (from 104 to 103 CFU 100 mL-1). The removal of E. coli was more strongly linked to luminosity and temperature, while the removal of total coliforms was influenced by the presence of the selected micropollutants.

Health and lifestyle parameters in peripheral artery disease at two periods of the COVID-19 pandemic: comparison between men and women.

OBJECTIVE: This study analyzed the impact of sex on self-reported health and lifestyle parameters in peripheral artery disease patients at two periods of the COVID-19 pandemic. METHODS: In this longitudinal study, 99 patients with peripheral artery disease (53 men and 46 women) were evaluated during two periods of the COVID-19 pandemic ( i.e ., at onset: May to August 2020, and on follow-up: May to August 2021). Patients were interviewed via telephone, and information regarding lifestyle and health parameters was obtained. RESULTS: At the onset of the COVID-19 pandemic, health and habit parameters were similar between women and men, with 63.0% and 45.3% indicating frequent fatigue, 73.9% and 84.9% reporting increased sitting time, and 23.9% and 39.6% practicing physical activity, respectively. At follow-up, difficulties in physical mobility (women: from 26.1% to 73.9%, p<0.001; men: from 39.6% to 71.7%, p=0.001) and the frequency of hospitalization for reasons other than COVID-19 increased similarly in women and men (women: from 4.3% to 21.7%, p=0.013; men: from 9.4% to 24.5%, p=0.038). The other parameters were similar between the periods. CONCLUSION: Self-reported physical mobility difficulties and hospitalization frequency increased in women and men with peripheral artery disease. BACKGROUND: ▪ Sitting time increased in 73.9% of women and 84.9% of men at the onset of the pandemic. BACKGROUND: ▪ Physical activity was practiced by 23.9% of women and 39.6% of men at the onset of the pandemic. BACKGROUND: ▪ The prevalence of both women and men reporting physical mobility difficulties increased at follow-up. BACKGROUND: ▪ Hospitalization rates for reasons unrelated to COVID-19 have increased in both women and. BACKGROUND: While women experience more consequences related to peripheral artery disease than men, such as worse functional capacity and higher morbidity, there was a similar increase in physical mobility difficulty and frequency of hospitalization for reasons other than COVID-19 one year after the onset of the pandemic.

Caloric Restriction Rejuvenates Skeletal Muscle Growth in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a major clinical problem, with limited treatments. HFpEF is characterized by a distinct, but poorly understood, skeletal muscle pathology, which could offer an alternative therapeutic target. In a rat model, we identified impaired myonuclear accretion as a mechanism for low myofiber growth in HFpEF following resistance exercise. Acute caloric restriction rescued skeletal muscle pathology in HFpEF, whereas cardiac therapies had no effect. Mechanisms regulating myonuclear accretion were dysregulated in patients with HFpEF. Overall, these findings may have widespread implications in HFpEF, indicating combined dietary with exercise interventions as a beneficial approach to overcome skeletal muscle pathology.

Seroprevalence of dengue IgG and associated risk factors in symptomatic and asymptomatic adults in Posadas (Misiones, Argentina), 2017-2019.

BACKGROUND: Dengue represents a major public health problem in the Americas in general, and in Posadas (Misiones, Argentina) in particular. This study aimed to assess the seroprevalence of dengue virus infection, analyze associated factors, and determine the proportion of asymptomatic cases. METHODS: This prospective cross-sectional study took place from November 2017 to April 2019 in the High Complexity Laboratory of Misiones, at the School Hospital Dr. Ramón Madariaga in Posadas. A random sample of 301 adults (≥ 15 years) was selected from the electoral registry and stratified by geographical area of residence. Sociodemographic, clinical, and laboratory data were collected by means of a survey and serology. Results were analyzed using multivariable logistic regression. RESULTS: The median age of the sample was 33 years; 66% were women, and 46.5% had completed at least secondary school. Anti-dengue IgG antibodies were present in 40.2% of the sample (95% confidence interval [CI] 34.5-45.9%), including 90% of those who reported dengue and 20.5% who did not (odds ratio [OR] 33.25, 95% CI 15.46-71.51, p < 0.001). In the multivariable analysis, adjusted for age, group, gender, and vaccination against yellow fever, seropositivity was associated with having relatives with dengue (adjusted OR 3.96, 95% CI 2.18-7.23; p < 0.001). CONCLUSION: Seroprevalence for dengue in Posadas was higher than estimates based on the notification records, and there was a high proportion of asymptomatic cases. Educational level and having a family member who had suffered from dengue were associated with positive serology.

Investigating the uses of machine learning algorithms to inform risk factor analyses: The example of avian infectious bronchitis virus (IBV) in broiler chickens.

Infectious bronchitis virus (IBV) is a contagious coronavirus causing respiratory and urogenital disease in chickens and is responsible for significant economic losses for both the broiler and table egg layer industries. Despite IBV being regularly monitored using standard epidemiologic surveillance practices, knowledge and evidence of risk factors associated with IBV transmission remain limited. The study objective was to compare risk factor modeling outcomes between a traditional stepwise variable selection approach and a machine learning-based random forest Boruta algorithm using routinely collected IBV antibody titer data from broiler flocks. IBV antibody sampling events (n = 1111) from 166 broiler sites between 2016 and 2021 were accessed. Ninety-two geospatial-related and poultry-density variables were obtained using a geographic information system and data sets from publicly available sources. Seventeen and 27 candidate variables were screened to potentially have an association with elevated IBV antibody titers according to the manual selection and machine learning algorithm, respectively. Selected variables from both methods were further investigated by construction of multivariable generalized mixed logistic regression models. Six variables were shortlisted by both screening methods, which included year, distance to urban areas, main roads, landcover, density of layer sites and year, however, final models for both approaches only shared year as an important predictor. Despite limited significance of clinical outcomes, this work showcases the potential of a novel explorative modeling approach in combination with often unutilized resources such as publicly available geospatial data, surveillance health data and machine learning as potential supplementary tools to investigate risk factors related to infectious diseases.

Herbicides in the initial growth and chlorophyll indices of sugarcane in pre-sprouted seedlings.

The aim of the present study was to assess the selectivity of herbicides applied in the pre and post-planting of pre-sprouted seedlings (PSS). The experiment was conducted in a greenhouse, using a completely randomized design, with nine treatments and four repetitions. The IACSP95-5000 cultivar was used. The treatments consisted of herbicides applied in five doses as follows: in pre-planting: sulfentrazone, diclosulam, imazapic, and imazapyr, in post-planting: ethoxysulfuron, halosulfuron, 2,4-D and MSMA, and a control treatment without herbicide. Injury symptoms were assessed at 7, 15, 30, 45, 60, 75, and 90 days after application (DAA), height, diameter, number of tillers, chlorophyll A, B, and total chlorophyll at 30, 60, and 90 DAA, leaf area, shoot and root dry mass at 90 DAA. The post-emergent herbicides were considered selective. Pre-planting herbicides reduced the variables assessed at 90 DAA, observed by linear regression for diclosulam and imazapic, and exponential regression for imazapyr. Treatments with sulfentrazone caused few injury symptoms, with subsequent recovery. In addition, all the variables analyzed were equal to control, with the sulfentrazone considered selective for the IACSP95-5000 cultivar.

Achieving rapid and significant results in healthcare services by using the theory of constraints.

Lack of timeliness and capacity are seen as fundamental problems that jeopardise healthcare delivery systems everywhere. Many believe the shortage of medical providers is causing this timeliness problem. This action research presents how one doctor implemented the theory of constraints (TOC) to improve the throughput (quantity of patients treated) of his ophthalmology imaging practice by 64% in a few weeks with little to no expense. The five focusing steps (5FS) guided the TOC implementation - which included the drum-buffer-rope scheduling and buffer management - and occurred in a matter of days. The implementation provided significant bottom-line results almost immediately. This article explains each step of the 5FS in general terms followed by specific applications to healthcare services, as well as the detailed use in this action research. Although TOC successfully addressed the practice problems, this implementation was not sustained after the TOC champion left the organisation. However, this drawback provided valuable knowledge. The article provides insightful knowledge to help readers implement TOC in their environments to provide immediate and significant results at little to no expense.

Immunotherapeutic Properties of Dexmedetomidine on Pain Management and Cardiovascular Function in Videolaparoscopic Cholecystectomies: A Randomized, Two-Arm, Double-Blinded, Placebo-Controlled Trial.

BACKGROUND: Laparoscopy represented one of the most innovative surgical techniques approached in the surgery field. Dexmedetomidine association with general anesthesia promotes the response control to trauma by altering the neuroinflammatory reflex, provides better clinical outcomes in the postoperative period and reduces the excessive use of drugs with risk for addiction. This trial aims to evaluate the potential drug treatment of dexmedetomidine on organic function, with the targets in neuroinflammation, perioperative pain control and blood pressure measurements in a medium-sized surgical model. METHODS: Fifty-two patients were randomized in two groups: Sevoflurane and Dexmedetomidine - A (dexmedetomidine infusion [1 µg/kg loading, .2-.5 µg/kg/h thereafter]) vs Sevoflurane and Saline .9% - B. Three blood samples were collected at three times: before surgery, 4 to 6 hours after surgery and 24 hours postoperatively. The primary outcome was inflammatory and endocrine mediators dosage analisys. Finally, we evaluated pain and opioid use as secondary outcomes, also the hemodynamic values. RESULTS: In Dexmedetomidine group A, a reduction of Interleukin 6 was found during 4-6 hours after surgery. A reduction of IL-10 was noted in the measurement of its values 24 hours after the procedure, with statistical significance. Also, systolic and diastolic blood pressure, as well heart rate were attenuated, and there was a lower incidence of pain and opioid consumption in the first postoperative hour (P < .0001) in the anesthetic recovery room. CONCLUSIONS: Dexmedetomidine provided anti-inflammatory activity, sympatholytic effect and analgesia with cardiovascular safety. It reinforces the therapeutic nature of highly selective α2-adrenergic agonists when combined within anesthetic interventions.

Spectroscopic behavior of bufotenine and bufotenine N-oxide: Solvent and pH effects and interaction with biomembrane models.

Bufotenine is a fluorescent analog of Dimethyltryptamine (DMT) that has been widely studied due to its psychedelic properties and biological activity. However, little is known about its spectroscopic properties in different media. Thus, we present in this work, for the first time, the spectroscopic behavior of bufotenine and bufotenine N-oxide by means of their fluorescence properties. Both molecules exhibit changes in optical absorption and emission spectra with variations in pH of the medium and in different solvents. Assays in the presence of biomembranes models, like micelles and liposomes, were also performed. In surfactants titration experiments, the spectral shift observed in fluorescence shows the interaction of both molecules with pre-micellar structures and with micelles. Steady state anisotropy measurements show that both bufotenine and bufotenine N-oxide, in the studied concentration range, interact with liposomes without causing changes in the fluidity of the lipid bilayer. These results can be useful in studies that aim at searching for new compounds, inspired by bufotenine and bufotenine N-oxide, with relevant pharmacological activities and also in studies that use these molecules as markers of psychiatric disorders.

Cactus species and tree forage hay in the diet of dairy goats.

The purpose of this study was to evaluate the influence of the association of Opuntia stricta (OS) or Nopalea cochenillifera (NC) with Moringa hay (MY) or Leucaena hay (LY) on nutrient intake, ingestive behavior, serum biochemistry, and milk production and composition of dairy goat. Eight multiparous Saanen goats were used, with an average of 68 ± 8 days in milk and 48.5 ± 6 kg of initial weight, fed with the following treatment diets: OS + MY; OS + LY; NC + MY, and NC + LY. The treatments were distributed in a double Latin square, in a 2 × 2 factorial scheme (two varieties of cactus and two of hay). Goats fed with NC had higher (P < 0.05) intakes of dry matter, crude protein, neutral detergent fiber (NDF), and non-fibrous carbohydrates. There was no influence (P > 0.05) on milk production, but goats fed with OS produced milk with higher (P < 0.05) fat content and presented higher (P < 0.05) feed efficiency. There was no effect (P > 0.05) of the hay type on the nutrient intake and milk production and composition of goats, but the animals fed with MY had higher (P < 0.05) serum cholesterol levels and greater efficiency of NDF rumination. Goats fed with OS showed greater feeding and rumination efficiency. Our results indicated that both cactus species could be successfully included in the diet of low yielding dairy goats fed 18.4% concentrate.