Novel Directed Enzyme Prodrug Therapy for Cancer Treatment Based on 2'-Deoxyribosyltransferase-Conjugated Magnetic Nanoparticles.

Directed enzyme prodrug therapy (DEPT) strategies show promise in mitigating chemotherapy side effects during cancer treatment. Among these, the use of immobilized enzymes on solid matrices as prodrug activating agents (IDEPT) presents a compelling delivery strategy, offering enhanced tumor targeting and reduced toxicity. Herein, we report a novel IDEPT strategy by employing a His-tagged Leishmania mexicana type I 2'-deoxyribosyltransferase (His-LmPDT) covalently attached to glutaraldehyde-activated magnetic iron oxide nanoparticles (MIONPs). Among the resulting derivatives, PDT-MIONP3 displayed the most favorable catalyst load/retained activity ratio, prompting its selection for further investigation. Substrate specificity studies demonstrated that PDT-MIONP3 effectively hydrolyzed a diverse array of 6-oxo and/or 6-amino purine 2'-deoxynucleosides, including 2-fluoro-2'-deoxyadenosine (dFAdo) and 6-methylpurine-2'-deoxyribose (d6MetPRib), both well-known prodrugs commonly used in DEPT. The biophysical characterization of both MIONPs and PDT-MIONPs was conducted by TEM, DLS, and single particle ICPMS techniques, showing an ideal nanosized range and a zeta potential value of -47.9 mV and -78.2 mV for MIONPs and PDT-MIONPs, respectively. The intracellular uptake of MIONPs and PDT-MIONPs was also determined by TEM and single particle ICPMS on HeLa cancer cell lines and NIH3T3 normal cell lines, showing a higher intracellular uptake in tumor cells. Finally, the selectivity of the PDT-MIONP/dFAdo IDEPT system was tested on HeLa cells (24 h, 10 µM dFAdo), resulting in a significant reduction in tumoral cell survival (11% of viability). Based on the experimental results, PDT-MIONP/dFAdo presents a novel and alternative IDEPT strategy, providing a promising avenue for cancer treatment.

Guided versus non-guided chin repositioning: a retrospective study on accuracy.

Genioplasty is a widely used surgical approach to address chin deformities by performing an osteotomy on the inferior border of the mandible to allow for comprehensive repositioning of the chin. This study aimed to compare the accuracy of freehand chin repositioning with a guided technique that employed specialised surgical guides. For this retrospective study, data from 30 adult patients who underwent orthognathic surgery to correct dentofacial deformities were analysed. All patients underwent virtual planning before surgery, with half of them treated using freehand chin repositioning and the other half using the guided technique. The surgical outcomes were measured and compared with the virtual plan to assess the positional and rotational accuracy of the techniques. In terms of translational assessment, noteworthy values that exceeded clinically acceptable limits were observed only in sagittal movement in the freehand group (0.97 mm, interquartile range (IQR) 0.73-2.29 mm). Regarding rotational accuracy, both groups exhibited an IQR that surpassed acceptable limits for pitch (3.26°, IQR 2.06-5.20 for the guided group and 2.57°, IQR 1.63-4.24° for the freehand group). The Mann-Whitney test indicated no statistical differences between the groups in any translational or rotational assessment. In conclusion, although there was no statistical difference, the guided technique proved effective in achieving clinically acceptable accuracy in all positions and almost all rotations, displaying superior results in sagittal positioning compared with the freehand technique. To fully harness the advantages of guides and to guarantee accuracy in all rotations, we recommend further research involving guides made of more rigid materials, and customised implants.

Coronene-Based 2D Networks by On-Surface Skeletal Rearrangement of Sumanene Precursors.

The design of novel low-dimensional carbon materials is at the forefront of modern chemistry. Recently, on-surface covalent synthesis has emerged as a powerful strategy to synthesize previously precluded compounds and polymers. Here, we report a scanning probe microscopy study, complemented by theoretical calculations, about the sequential skeletal rearrangement of sumanene-based precursors into a coronene-based organometallic network by stepwise intra- and inter-molecular reactions on Au(111). Interestingly, upon higher annealing, the formed organometallic networks evolve into two-dimensional coronene-based covalently-linked patches through intermolecular homocoupling reactions. A new reaction mechanism is proposed based on the role of C-Au-C motifs to promote two stepwise carbon-carbon couplings to form cyclobutadiene bridges. Our results pave avenues for the conversion of molecular precursors on surfaces, affording the design of unexplored two-dimensional organometallic and covalent materials.

The Impact of Metolachlor Applications and Phytoremediation Processes on Soil Microorganisms: Insights from Functional Metagenomics Analysis.

This study assessed the impact of phytoremediation on reducing the residual concentration of metolachlor in soil treated with doses of 530.7 and 1061.4 g/ha and its effect on microbial biodiversity in contaminated areas. For the plant species Avena sativa and Medicago sativa, a significant efficacy of 54.5 and 36.4% was observed in the dissipation of the herbicide, especially at higher doses. Although metolachlor application reduced soil microbial biodiversity, phytoremediating plants, especially M. sativa, promoted greater richness and distribution of microbial species, mitigating the negative effects of the herbicide. Principal component analysis revealed the influence of these plants and metolachlor on the composition of the microbial community. These results highlight the importance of phytoremediation in promoting soil biodiversity and reducing herbicide contamination, providing crucial insights for remediation strategies in contaminated areas.

Redefining Statin Dosage Post-Gastric Bypass: Insights from a Population Pharmacokinetics-Pharmacodynamics Link Approach.

Roux-en-Y gastric bypass (RYGB) involves creating a small stomach pouch, bypassing part of the small intestine, and rerouting the digestive tract. These alterations can potentially change the drug exposure and response. Our primary aim was to assess the impact of RYGB on the pharmacokinetics of simvastatin lactone (SV) and its active metabolite, simvastatin hydroxy acid (SVA). Ultimately, we aimed to optimize dosing for this understudied population by employing a population pharmacokinetic-pharmacodynamic link approach. The study comprised patients who had undergone RYGB surgery and individuals without a previous history of RYGB. All participants received a single oral dose of simvastatin. Plasma concentration data were analyzed with a nonlinear mixed-effect modeling approach. A parent-metabolite model with first-order absorption, 2-compartments for SV and 1-compartment for SVA, linear elimination, and enterohepatic circulation best described the data. The model was linked to the turnover pharmacodynamic model to describe the SVA inhibition on LDL-cholesterol production. Our simulations indicated that following RYGB surgery, the exposure to SV and SVA decreased by 40%. Consequently, for low-intensity statin patients, we recommend increasing the dose from 10 to 20 mg in post-RYGB patients to maintain a comparable response to that of non-operated subjects. Moderate-intensity statin patients should require increasing doses to 40 or 60 mg or the addition of a non-statin medication to achieve similar therapeutic outcomes. In conclusion, individuals post-RYGB exhibit diminished exposure to SV and may benefit from increasing the dose or adjunctive therapy with non-statin drugs to attain equivalent responses and mitigate potential adverse events.

Anti-obesogenic effect of lupin-derived protein hydrolysate through modulation of adiposopathy, insulin resistance and gut dysbiosis in a diet-induced obese mouse.

The prevalence of obesity is increasingly widespread, resembling a global epidemic. Lifestyle changes, such as consumption of high-energy-dense diets and physical inactivity, are major contributors to obesity. Common features of this metabolic pathology involve an imbalance in lipid and glucose homeostasis including dyslipidemia, insulin resistance and adipose tissue dysfunction. Moreover, the importance of the gut microbiota in the development and susceptibility to obesity has recently been highlighted. In recent years, new strategies based on the use of functional foods, in particular bioactive peptides, have been proposed to counteract obesity outcomes. In this context, the present study examines the effects of a lupin protein hydrolysate (LPH) on obesity, dyslipidemia and gut dysbiosis in mice fed a high-fat diet (HFD). After 12 weeks of LPH treatment, mice gained less weight and showed decreased adipose dysfunction compared to the HFD-fed group. HFD-induced dyslipidemia (increased triglycerides, cholesterol and LDL concentration) and insulin resistance were both counteracted by LPH consumption. Discriminant analysis differentially distributed LPH-treated mice compared to non-treated mice. HFD reduced gut ecological parameters, promoted the blooming of deleterious taxa and reduced the abundance of commensal members. Some of these changes were corrected in the LPH group. Finally, correlation analysis suggested that changes in this microbial population could be responsible for the improvement in obesity outcomes. In conclusion, this is the first study to show the effect of LPH on improving weight gain, adiposopathy and gut dysbiosis in the context of diet-induced obesity, pointing to the therapeutic potential of bioactive peptides in metabolic diseases.

Pharmacological inhibition of CK2 by silmitasertib mitigates sepsis-induced circulatory collapse, thus improving septic outcomes in mice.

Casein kinase II (CK2) has recently emerged as a pivotal mediator in the propagation of inflammation across various diseases. Nevertheless, its role in the pathogenesis of sepsis remains unexplored. Here, we investigated the involvement of CK2 in sepsis progression and the potential beneficial effects of silmitasertib, a selective and potent CK2α inhibitor, currently under clinical trials for COVID-19 and cancer. Sepsis was induced by caecal ligation and puncture (CLP) in four-month-old C57BL/6OlaHsd mice. One hour after the CLP/Sham procedure, animals were assigned to receive silmitasertib (50 mg/kg/i.v.) or vehicle. Plasma/organs were collected at 24 h for analysis. A second set of experiments was performed for survival rate over 120 h. Septic mice developed multiorgan failure, including renal dysfunction due to hypoperfusion (reduced renal blood flow) and increased plasma levels of creatinine. Renal derangements were associated with local overactivation of CK2, and downstream activation of the NF-ĸB-iNOS-NO axis, paralleled by a systemic cytokine storm. Interestingly, all markers of injury/inflammation were mitigated following silmitasertib administration. Additionally, when compared to sham-operated mice, sepsis led to vascular hyporesponsiveness due to an aberrant systemic and local release of NO. Silmitasertib restored sepsis-induced vascular abnormalities. Overall, these pharmacological effects of silmitasertib significantly reduced sepsis mortality. Our findings reveal, for the first time, the potential benefits of a selective and potent CK2 inhibitor to counteract sepsis-induced hyperinflammatory storm, vasoplegia, and ultimately prolonging the survival of septic mice, thus suggesting a pivotal role of CK2 in sepsis and silmitasertib as a novel powerful pharmacological tool for drug repurposing in sepsis.

Undisturbed culture: a clinical examination of this culture strategy on embryo in vitro development and clinical outcomes.

OBJECTIVE: To compare the effect of a fully undisturbed culture strategy over a sequential one on embryo in vitro development and clinical outcomes in intracytoplasmic sperm injection (ICSI) cycles. DESIGN: Retrospective cohort study. SETTING: University-affiliated private IVF center. PATIENT(S): This study included 4,564 ICSI cycles performed over 5 years, including autologous and oocyte donation treatments with extended embryo culture until blastocyst in one of the two defined culture strategies. INTERVENTION(S): Embryo cohorts were cultured in one of two culture systems: a fully undisturbed culture, including an incubator with integrated time-lapse technology, a one-step culture medium and embryo selection assisted by semi-automatic tools on the basis of embryo morphokinetics, or a sequential culture, using a conventional benchtop incubator, sequential media and traditional morphological evaluation under optical microscope. The effect of the culture strategies on embryo development and clinical outcomes was quantified by generalized estimated equations, controlling for possible confounders through the inverse probability of the treatment weighting method. MAIN OUTCOME MEASURE(S): Weighted odds ratios (ORs) and 95% confidence intervals (CIs) for live birth rate after fresh single embryo transfer and the cumulative live birth rate. In addition, blastocyst development and morphology and other intermediate outcomes were also assessed. RESULT(S): A significant positive association was found between the employment of undisturbed embryo culture and higher live birth rate in the first embryo transfer in both autologous (OR, 1.617; 95% CI, 1.074-2.435) and oocyte donation cycles (OR, 1.316; 95% CI, 1.036-1.672). Cumulative live birth rate after 1-year follow-up was also positively associated with the undisturbed culture strategy in oocyte donation cycles (OR, 1.5; 95% CI, 1.179-1.909), but not in autologous cycles (OR, 1.051; 95% CI, 0.777-1.423). Similarly, blastocyst rate, good morphology blastocyst rate, and utilization rate were positively associated with the employment of undisturbed culture in oocyte donation cycles, but not in autologous cycles. CONCLUSION(S): These findings imply that a culture system combining integrated time-lapse incubators with a one-step culture medium may enhance the success rates of patients undergoing ICSI treatment by increasing the production of higher quality blastocysts and improving embryo selection while streamlining laboratory procedures and workflow.

Dual-task training is as effective as functional training on the functional fitness of older women: a randomized clinical trial.

BACKGROUND: The interest in approaches that improve older individuals' functional fitness and autonomy is increasing. However, the effects of dual-task training on older women's functional fitness and the comparison with the functional training approach are unclear. Therefore, we compared dual-task and functional training on the functional fitness of older women and the effects of three months of detraining. METHODS: Sixty-one women performed 16 weeks of dual-task training or functional training. The functional fitness was measured pre-, post-training, and post-detraining, based on the ability to put on and take off a t-shirt, evaluating the mobility of the upper limb, standing-up from the prone position measuring the global functionality, five times sit-to-stand test to assess the lower limbs muscle power, timed up and go to measure the dynamic balance and agility, gallon-jug shelf-transfer to evaluate the global functionality emphasizing the upper limbs and 10 m walk test to analyze the gait ability. RESULTS: Dual-task training and functional training generally provided significant small to moderate magnitude performance increases in the put on and take off a t-shirt (dual-task training: d = 0.35 / functional training: d = 0.49), five times sit-to-stand test (dual-task training: d = 0.41 / functional training: d = 0.77), timed up and go (dual-task training: d = 0.34 / functional training: d = 0.78), and gallon-jug shelf-transfer (dual-task training: d = 0.76 / functional training: d = 0.82). Only the functional training improved the 10 m walk test (d = 0.32; p = 0.013), and both groups did not change the standing-up from the prone position performance. After the detraining period, both groups kept the adaptations for the gallon-jug shelf-transfer and five times sit-to-stand test. At the same time, only the dual-task training maintained the adaptations for the put on and take off a t-shirt and the functional training for the timed up and go. CONCLUSION: Sixteen weeks of dual-task and functional training are similarly effective in improving older women's functional fitness, maintaining their benefits even after three months of detraining. TRIAL REGISTRATION: RBR-10ny848z ( https://ensaiosclinicos.gov.br/rg/RBR-10ny848z ).

Quality of Care Transition for COVID-19 Patients in a University Hospital in Southern Brazil.

OBJECTIVE: To assess the quality of care transition from hospital to home for COVID-19 patients. METHOD: A cross-sectional study conducted at a University Hospital in Southern Brazil, involving 78 patients discharged after COVID-19 hospitalization. Data collection was performed via telephone using the Brazilian version of the Care Transitions Measure (CTM-15). Data were analyzed using descriptive and analytical statistics. RESULTS: The mean quality of care transition was 70.8 on a scale ranging from zero to 100, indicating moderate quality of care transition. The highest score was attributed to factor 1, "Preparation for self-management," and the lowest to factor 4, "Care Plan." CONCLUSIONS: It is important to enhance communication and support provided to patients during the transition process, especially regarding understanding prescribed medications and the development of clear care plans.

Characteristics of surveillance systems for suicide and self-harm: A scoping review.

BACKGROUND: Suicide is a complex public health issue. Surveillance systems play a vital role in identifying trends and epidemiologic needs, informing public health strategies, and tailoring effective context-based suicide prevention interventions. AIM: To identify and summarise the characteristics of specific surveillance systems and general health behaviour that include data onsuicide and self-harm. METHOD: A scoping review following the JBI recommendations and PRISMA-ScR guidelines identified 29 relevant studies on suicide and self-harm surveillance systems. A systematic search was performed on Cinahl, Embase, Lilacs-Latin American and Caribbean Health Sciences Literature, PubMed-US National Library of Medicine, Scopus, and Google Scholar. The eligibility criteria include papers that use qualitative, quantitative or mixed methods with no restrictions on time or language. The following papers were excluded regarding euthanasia and assisted suicide, as well as papers that did not explicitly describe suicide, self-harm, and surveillance systems. Two researchers independently screened the materials for eligibility and extracted data from the included studies. Data analysis was conducted using content analysis. RESULTS: Twenty-nine references were included, and 30 surveillance systems were identified and classified into general health behaviour surveillance (n = 15) and specific systems for suicide and self-harm (n = 15). General health behaviour systems often operate at national data collection level, collecting non-fatal data in healthcare settings, mainly emergency departments. The specific systems exhibited greater variability in terms of context, involved actors, data collection level, data collection procedures, and case classification. Limitations found by the studies pointed mostly to case definitions and data quality. Co-production, intersectoral collaboration, clear case definition criteria and data standardisation are essential to improve surveillance systems for suicide and self-harm. CONCLUSIONS: This review identified the characteristics of surveillance systems for suicide and self-harm. Monitoring and evaluation are crucial for ongoing relevance and impact on prevention efforts.

Rhizosphere-associated microbiota of Canavalia ensiformis in sulfentrazone bioremediation.

The objective of this study was to determine the efficiency of the microbial rhizosphere (Canavalia ensiformis) in the phytoremediation of sulfentrazone using quantification methods (CO2 evolution, microbial biomass carbon, and metabolic quotient) and identification of bacteria (PCR-DGGE technique). The experiment was conducted in a completely randomized design, in a 2x4 factorial scheme, with four replications. The treatments were composed of rhizospheric soil (cultivated with C. ensiformis) and non-rhizosphere soil (uncultivated soil); and four levels of contamination by sulfentrazone (0, 200, 400, and 800 g ha-1 a.i.). The microbiota associated with the rhizosphere of C. ensiformis efficiently reduced sulfentrazone residues in the soil, with better performance at the dose of 200 g ha-1 a.i. Using the PCR-DGGE technique allowed the distinction of two profiles of bacteria in the rhizospheric activity of C. ensiformis. The second bacterial profile formed was more efficient in decontaminating soil contaminated with sulfentrazone residue. The microbiota associated with the rhizosphere of C. ensiformis has an efficient profile in decontaminating soils with residues equivalent to 200 g ha-1 a.i. the herbicide sulfentrazone.

Phytoremediation of soils contaminated with herbicide residues is a viable technique for decontamination of the environment.Canavalia ensiformis has an efficient profile in the decontamination of soils with residue equivalent to 200 g ha⁻¹ a.i. of the herbicide sulfentrazone.The PCR technique and microbial respiration used to analyze the diversity and estimate the bacterial population of a soil are viable tools to evaluate the phytoremediation potential of the microbiota associated with plant species.

Influence of proportion of Brahman genetics on productivity of Brahman-Angus cows at weaning.

This study evaluated the association between the proportion of Brahman genetics and productivity of Brahman-Angus cows at weaning using a 31-yr dataset containing 6,312 cows and 5,405 pregnancies. Cows were contemporaneously reared and enrolled in yearly breeding seasons under subtropical conditions of North-Central Florida. They were evenly distributed in six-breed groups (G) according to the proportion of Brahman genetics: G0% to 19%, G21% to 34%, G38% (Brangus), G41% to 59%, G63% to 78%, and G81% to 100%. The proportion of cows calving (84.9%) did not differ across the six-breed groups. However, cows in the G81% to 100% weaned fewer calves (90.8%) than cows in the G0% to 19% and G21% to 34% (95.7%, each). The weaning rate of cows in the G38% (94.3%), G41% to 59% (94.2%), and G63% to 78% (93.0%) was intermediate between these three breed groups. The preweaning calf mortality was greater for cows in the G81% to 100% (9.2%) than cows in the G0% to 19% and G21% to 34% (4.3%, each), but intermediate for cows in the G38% (5.7%), G41% to 59% (5.8%), and G63% to 78% (7.0%). Cows in the G81% to 100% also weaned lighter calves (220.6 kg) than cows in the G0% to 19% (245.2 kg), G21% to 34% (250.2 kg), G38% (247.9 kg), G41% to 59% (252.5 kg), and G63% to 78% (245.2 kg). Cows in the G0% to 19% weaned lighter calves than cows with 21% to 78% of Brahman genetics. The 205-d adjusted weaning weight evidenced the less productive results of cows in G0% to 19% and G81% to 100% compared with other genetic groups, as they calved at the fastest and slowest rate, respectively. Thus, the 205-d adjusted weaning weight eliminated this bias. Additionally, younger cows weaned lighter calves; and male calves were heavier at weaning than female calves. Both parity order of cow and calf sex altered the magnitude of the described association between breed group of cows and calf weaning weights. Overall, after adjusting for weaning rate and age of calves at weaning, the number of kilograms produced per cow submitted to reproduction was less for cows in the G0% to 19% (191.1 kg) and G81% to 100 (181.8 kg) compared with cows in the G21% to 34 (197.0 kg), G38 (195.9 kg), G41% to 59 (199.7), and G63% to 78 (196.2). Cows in the G81% to 100% were the least productive. Thus, a proportion of Brahman genetics between 21% and 78% ensured superior productivity of Brahman-Angus cows subjected to subtropical conditions.

Effectiveness of two scrub methods with different chlorhexidine combinations for surgical field antisepsis in cats.

Objective: Assessing effectiveness of circular (CM) and linear (LM) scrub methods using 3 different combinations of chlorhexidine in surgical field antisepsis in cats. Animals and procedure: Surgical field antisepsis was applied with 2 scrub methods (CM and LM) and 3 different chlorhexidine combinations (A1, A2, and A3) in 51 female cats undergoing ovariectomy. Sterile swabs collected from the surgical field pre- and post-antisepsis were inoculated in the laboratory and colony-forming units (CFU/mL) were quantified. Results: Following the application of antisepsis, the number of positive samples decreased in all groups (P < 0.05) when using both CM and LM, except for CM in the A1 group (P = 0.063). The CFU/mL counts also decreased after antisepsis with both CM and LM in all groups (P < 0.05). A high reduction in CFU/mL counts was observed after antisepsis with both CM and LM in all groups, but no significant differences were observed between the 2 scrub methods (P > 0.05). Conclusion and clinical relevance: Surgical field antisepsis in cats with CM and LM scrub methods, using 2% chlorhexidine combined with 70% ethyl or 70% isopropyl alcohol, or 1% chlorhexidine combined with 70% ethyl alcohol, can effectively reduce the bacterial load on the skin.

Efficacité de deux méthodes de désinfection avec différentes combinaisons de chlorhexidine pour l'antisepsie du champ opératoire chez le chat. Objectif: Évaluation de l'efficacité des méthodes de désinfection par mouvements circulaires (CM) et linéaires (LM) utilisant 3 combinaisons différentes de chlorhexidine dans l'antisepsie du champ opératoire chez le chat. Animaux et procédure: Une antisepsie chirurgicale sur le terrain a été appliquée avec 2 méthodes de désinfection (CM et LM) et 3 combinaisons différentes de chlorhexidine (A1, A2 et A3) chez 51 chattes subissant une ovariectomie. Des écouvillons stériles prélevés sur le champ opératoire avant et après l'antisepsie ont été inoculés en laboratoire et les unités formant des colonies (UFC/mL) ont été quantifiées. Résultats: À la suite de l'application de l'antisepsie, le nombre d'échantillons positifs a diminué dans tous les groupes (P < 0,05) lors de l'utilisation à la fois de CM et de LM, à l'exception du CM dans le groupe A1 (P = 0,063). Le nombre d'UFC/mL a également diminué après antisepsie avec CM et LM dans tous les groupes (P < 0,05). Une forte réduction du nombre d'UFC/mL a été observée après antisepsie avec CM et LM dans tous les groupes, mais aucune différence significative n'a été observée entre les 2 méthodes de désinfection (P > 0,05). Conclusion et pertinence clinique: L'antisepsie chirurgicale sur le terrain chez les chats avec les méthodes de désinfection CM et LM, utilisant 2 % de chlorhexidine combinée à 70 % d'alcool éthylique ou 70 % d'alcool isopropylique, ou 1 % de chlorhexidine combinée à 70 % d'alcool éthylique, peut réduire efficacement la charge bactérienne sur la peau.(Traduit par Dr Serge Messier).

World Heart Federation Cholesterol Roadmap: The Portuguese case.

Atherosclerotic cardiovascular disease (ASCVD) remains the major cause of premature death and disability; effective cardiovascular (CV) risk prevention is fundamental. The World Heart Federation (WHF) Cholesterol Roadmap provides a framework for national policy development and aims to achieve ASCVD prevention. At the invitation of the WHF, a group of experts from the Portuguese Society of Cardiology (SPC), addressed the cholesterol burden at nationally and discussed possible strategies to include in a Portuguese cholesterol roadmap. The literature review showed that the cholesterol burden in Portugal is high and especially uncontrolled in those with the highest CV risk. An infographic scorecard was built to include in the WHF collection, for a clear idea about CV risk and cholesterol burden in Portugal, which would also be useful for health policy advocacy. The expert discussion and preventive strategies proposal followed the five pillars of the WHF document: awareness improvement; population-based approaches for CV risk and cholesterol; risk assessment/population screening; system-level approaches; surveillance of cholesterol and ASCVD outcomes. These strategies were debated by all the expert participants, with the goal of creating a national cholesterol roadmap to be used for advocacy and as a guide for CV prevention. Several key recommendations were outlined: include all stakeholders in a multidisciplinary national program; create a structured activities plan to increase awareness in the population; improve the quality of continuous CV health education; increase the interaction between different health professionals and non-health professionals; increment the referral of patients to cardiac rehabilitation; screen cholesterol levels in the general population, especially high-risk groups; promote patient self-care, engage with patients' associations; use specific social networks to spread information widely; create a national database of cholesterol levels with systematic registry of CV events; redefine strategies based on the evaluation of results; create and involve more patients' associations - invert the pyramid order. In conclusion, ASCVD and the cholesterol burden remain a strong global issue in Portugal, requiring the involvement of multiple stakeholders in prevention. The Portuguese cholesterol roadmap can provide some solutions to help urgently mitigate the problem. Population-based approaches to improve awareness and CV risk assessment and surveillance of cholesterol and ASCVD outcomes are key factors in this change. A call to action is clearly needed to fight hypercholesterolemia and ASCVD burden.

Atypical phosphatase DUSP11 inhibition promotes nc886 expression and potentiates gemcitabine-mediated cell death through NF-kB modulation.

Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers among all solid tumors. First-line treatment relies on gemcitabine (Gem) and despite treatment improvements, refractoriness remains a universal challenge. Attempts to decipher how feedback-loops control signaling pathways towards drug resistance have gained attention in recent years, particularly focused on the role of phosphatases. In this study, a CRISPR/Cas9-based phenotypic screen was performed to identify members from the dual-specificity phosphatases (DUSP) family potentially acting on Gem response in PDAC cells. The approach revealed the atypical RNA phosphatase DUSP11 as a potential target, whose inhibition creates vulnerability of PDAC cells to Gem. DUSP11 genetic inhibition impaired cell survival and promoted apoptosis, synergistically enhancing Gem cytotoxicity. In silico transcriptome analysis of RNA-seq data from PDAC human samples identified NF-ĸB signaling pathway highly correlated with DUSP11 upregulation. Consistently, Gem-induced NF-ĸB phosphorylation was blocked upon DUSP11 inhibition in vitro. Mechanistically, we found that DUSP11 directly impacts nc886 expression and modulates PKR-NF-ĸB signaling cascade after Gem exposure in PDAC cells resulting in resistance to Gem-induced cell death. In conclusion, this study provides new insights on DUSP11 role in RNA biology and Gem response in PDAC cells.

Efficacy of aromatherapy with Lavandula angustifolia oil on postoperative pain after cardiac surgery: A randomized clinical trial.

OBJECTIVE: To evaluate the effect of aromatherapy through inhalation of Lavandula angustifolia essential oil in relieving pain during the immediate postoperative period of patients undergoing cardiac surgery. METHODS: A single-blind, randomized and controlled clinical trial, with 52 patients in the immediate postoperative period of cardiac surgery were randomly distributed into experimental (n = 26) and control (n = 26) groups. The primary outcome was whether or not pain was relieved and secondary outcomes included changes in vital signs, sleep and facial relaxation. The control group received industry standard care and application of an essential oil-free ceramic diffuser necklace. The experimental group received the inhalation intervention with pure Lavandula angustifolia essential oil, with a drop of the oil on a ceramic diffuser necklace at a distance of 15-20 cm from the patient's nose for 30 min. Pain was measured using the Numerical Visual Scale, and vital signs using the multiparametric monitor before the intervention, 10 minutes after its start and 30 minutes after the total end of inhalation. Face relaxation was assessed before and after the intervention and sleep was assessed at the end of inhalation. RESULTS: There was a decrease in pain levels (p < 0.001) 30 min after the end of inhalation in the Experimental Group, with a decrease in the measurements of Mean Blood Pressure (p= 0.008) and Respiratory Rate (p = 0.011). Furthermore, facial relaxation and sleep had a large effect size of 2.54 and 1.28, respectively. CONCLUSION: Lavandula angustifolia essential oil was effective in relieving pain, causing sleep and relaxation, proving to be a low-cost and easy-to-use tool that the nursing team can use in their care.

Cancer Prevention and Cultural Continuity for Métis Peoples in Canada: A Scoping Review.

The purpose of this scoping review was to map the literature on the relationship between cultural continuity and health among Métis people as well as how this knowledge could be translated into cancer prevention initiatives. We included any Métis-specific literature evaluating connections between culture, health, and well-being. We conducted electronic searches of Medline, PubMed, Embase, PsychInfo, I-Portal, and hand-searched journals, and reviewed the grey literature. Based on our inclusion criteria, articles were screened and assessed for eligibility, resulting in a sample of 22 publications. Qualitative, quantitative, and mixed methods designs were considered. The 22 publications included in this review were diverse, ranging from population-based studies to reports and news articles. There were no limitations to publication year, and most of the data presented in this review were published more than five years ago. Nevertheless, the results demonstrate the potential role of Métis cultural continuity in cancer prevention. The scoping review revealed the current lack of Métis-specific data regarding health and its intersectionality with culture. However, the existing literature indicates that cultural continuity for Métis appears to influence health and well-being positively. As such, there may be benefits to incorporating cultural continuity in cancer prevention efforts.

Clinical prediction scale approach derived from a retrospective study to reduce the number of urgent, low-value cranial CT scans.

PURPOSE: Fifty percent of cranial CT scans performed achieve no benefit and entail risks. Our aim is to determine the yield of non-traumatic urgent cranial-CT and develop a pretest clinical probability scale approach. METHODS: Adult patients seen in our emergency department between 2017-2021 and referred for urgent cranial-CT for non-traumatic reasons were retrospectively recruited and randomly selected. Presenting complaint (PC), demographic variables, Relevant radiological findings (RRF) on the urgent cranial-CT and Relevant clinical-radiological findings (RCRF: admission need or RRF detection on the urgent cranial-CT or cranial CT/MRI in the following three months) were recruited. RESULTS: We recruited 702 patients, with median age 62 [47-76] years, 363 (51.7%) females. RCRF were observed in 404 (57.55%); of these, 352 (50.1%) required admission. RRF were detected in 190 (27.06%): 36 acute ischemic and 27 acute hemorrhagic lesions, 115 masses, 9 edema, and 27 hydrocephalus. Predictive PC for urgent cranial-CT were motor, speech, sensory deficits, sudden alteration of mental status, epileptic seizure, cognitive impairment, neurological symptoms in cancer patients, acute headache without a prior history and with meningeal signs; nausea, vomiting, or hypertensive crisis; visual deficits, and dizziness. This algorithm provided sensitivity, specificity, positive predictive value, and negative predictive value (NPV, 95%CI in brackets) of 92.1% (89-94.5%), 27.5% (22.5-33.0%), 63.3% (59.2-67.2%), and 71.9% (62.7-80.0%), to diagnose RCRF, and 97.4% (93.4-99.1%), 21.3% (17.8-25.1%), 31.5% (27.7-35.4%), and 95.6% (90.1-98.6%), to diagnose RRF. In patients not requiring admission (n = 350), the NPV for RRF was 98.8% (93.6-100%); the negative likelihood ratio 0.08 (0.01-0.57), and sensitivity remained at 97.8% (82.2-99.9%). Applying it would have avoided performing 85/350 urgent cranial-CT (24.29%). To find one RRF, we would have gone from performing 7.8 (350/45) to 5.9 (265/45) CTs, failing to diagnose 1/45 (2.2%) RRF. CONCLUSIONS: This proposed clinical scale could potentially decrease 24% of urgent cranial-CT.

Adherence to standard precautions in university hospitals during the COVID-19 pandemic: a mixed study.

OBJECTIVE: To analyze adherence to standard precautions by healthcare professionals and associated factors during the COVID-19 pandemic in Brazilian university hospitals. METHOD: Multicenter study, with a mixed approach, with a concomitant incorporated strategy and a sample of 559 health professionals and 53 managers from five university hospitals in Southern Brazil. Data collected online from September 2020 to October 2021 with the Instrument of Variables Related to Standard Precautions and sociodemographic and pandemic-related variables. Descriptive and inferential statistical analysis (Mann-Whitney and Kruskal-Wallis test) and content analysis were performed. RESULTS: High level of adherence to standard precautions, with a significant association with having children (p = 0.014); COVID area (p < 0.001), biosafety training (p = 0.018), and social distancing (p < 0.001). The testimonies demonstrated a high risk perception and search for the use of protective equipment and biosafety knowledge. CONCLUSION: High adherence to standard precautions, associated with having children, working in COVID-19 care units, receiving biosafety guidance/training at the institution and practicing social distancing.