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We present the development and characterization of a nasal drug delivery system comprised of a thermosensitive mucoadhesive hydrogel based on a mixture of the polymers Poloxamer 407, Poloxamer 188 and Hydroxypropyl-methylcellulose, and the psychedelic drug 5-methoxy-N,-N-dimethyltryptamine. The development relied on a 3 × 3 Box-Behnken experimental design, focusing on optimizing gelification temperature, viscosity and mucoadhesion. The primary objective of this work was to tailor the formulation for efficient nasal drug delivery. This would increase contact time between the hydrogel and the mucosa while preserving normal ciliary functioning. Following optimization, the final formulation underwent characterization through an examination of the in vitro drug release profile via dialysis under sink conditions. Additionally, homogeneity of its composition was assessed using Raman Confocal Spectroscopy. The results demonstrate complete mixing of drug and polymers within the hydrogel matrix. Furthermore, the formulation exhibits sustained release profile, with 73.76% of the drug being delivered after 5 h in vitro. This will enable future studies to assess the possibility of using this formulation to treat certain mental disorders. We have successfully developed a promising thermosensitive and mucoadhesive hydrogel with a gelling temperature of around 32 °C, a viscosity close to 100 mPas and a mucoadhesion of nearly 4.20 N·m.

During the last decade, immunotherapy has radically changed perspectives on anti-tumor treatments. However, solid tumor treatment by immunotherapy has not met expectations. Indeed, poor clinical response to treatment has highlighted the need to understand and avoid immunotherapy resistance. Cholangiocarcinoma (CCA) is the second cause of hepatic cancer-related deaths because of drug inefficacy and chemo-resistance in a majority of patients. Thus, intense research is ongoing to better understand the mechanisms involved in the chemo-resistance processes. The tumor microenvironment (TME) may be involved in tumor therapy resistance by limiting drug access. Indeed, cells such as cancer-associated fibroblasts (CAFs) alter TME by producing in excess an aberrant extracellular matrix (ECM). Interestingly, CAFs are the dominant stromal component in CCA that secrete large amounts of stiff ECM. Stiff ECM could contribute to immune exclusion by limiting anti-tumor T-cells drop-in. Herein, we summarize features, functions, and interactions among CAFs, tumor-associated ECM, and immune cells in TME. Moreover, we discuss the strategies targeting CAFs and the remodeling of the ECM to improve immunotherapy and drug therapies.

Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence.Methods: We undertook a drug discovery campaign against the essential major protease (MPro) from SARS-CoV-2, which relied on an in silico search strategy –performed in a large and diverse chemolibrary– complemented by experimental validation. The computational method comprises a recently reported ligand-based approach developed upon refinement/learning cycles, and structure-based approximations. Search models were applied to both retrospective (in silico) and prospective (experimentally confirmed) screening.Results: The first generation of ligand-based models were fed by data, which to a great extent, had not been published in peer-reviewed articles. The first screening campaign performed with 188 compounds (46 in silico hits and 100 analogues, and 40 unrelated compounds: flavonols and pyrazoles) yielded three hits against MPro (IC50 ≤ 25 μM): two analogues of in silico hits (one glycoside and one benzo-thiazol) and one flavonol. A second generation of ligand-based models was developed based on this negative information and newly published peer-reviewed data for MPro inhibitors. This led to 43 new hit candidates belonging to different chemical families. From 45 compounds (28 in silico hits and 17 related analogues) tested in the second screening campaign, eight inhibited MPro with IC50 = 0.12–20 μM and five of them also impaired the proliferation of SARS-CoV-2 in Vero cells (EC50 7–45 μM).Discussion: Our study provides an example of a virtuous loop between computational and experimental approaches applied to target-focused drug discovery against a major and global pathogen, reaffirming the well-known “garbage in, garbage out” machine learning principle.

Objective: To compare bioelectrical impedance analysis (BIA)-derived parameters in healthy volunteers and critically ill patients and to assess its prognostic value in an ICU patient cohort. Design: Retrospective, observational data analysis. Setting: Single centre, tertiary-level ICU (Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg Hospital). Patients: 101 patients and 101 healthy subjects, participants of International Fluid Academy Days. Measurements and main results: Compared to healthy volunteers, both male and female ICU patients had significantly higher values for total body water (TBW), extracellular water (ECW), extracellular fluid (ECF), plasma, and interstitial fluid volumes. The phase angle was significantly lower and the malnutrition index was significantly higher in ICU patients, regardless of gender. Non-survivors in the ICU had significantly higher extracellular water content (ECW, 50.7 ± 5.1 vs. 48.9 ± 4.3%, p = 0.047) and accordingly significantly lower intracellular water (ICW, 49.2 ± 5.1 vs. 51.1 ± 4.3%, p = 0.047). The malnutrition index was also significantly higher in non-survivors compared to survivors (0.94 ± 0.17 vs. 0.87 ± 0.16, p = 0.048), as was the capillary leak index (ECW/ICW). Conclusions: Compared to healthy volunteers, this study observed a higher malnutrition index and TBW in ICU patients with an accumulation of fluids in the extracellular compartment. ICU non-survivors showed similar results, indicating that ICU patients and a fortiori non-survivors are generally overhydrated, with increased TBW and ECW, and more undernourished, as indicated by a higher malnutrition index.

Abstract Background Dietary interventions have been previously explored in children with ADHD. Elimination diets and supplementation can produce beneficial behaviour changes, but little is known about the mechanisms mediating change. We propose that these interventions may work, in part, by causing changes in the gut microbiota. A microbiome-targeted dietary intervention was developed, and its feasibility assessed. Methods A non-randomised feasibility study was conducted on nine non-medicated children with ADHD, aged 8–13 years (mean 10.39 years), using a prospective one-group pre-test/post-test design. Participants were recruited from ADHD support groups in London and took part in the 6-week microbiome-targeted dietary intervention, which was specifically designed to impact the composition of gut bacteria. Children were assessed pre- and post-intervention on measures of ADHD symptomatology, cognition, sleep, gut function and stool-sample microbiome analysis. The primary aim was to assess the study completion rate, with secondary aims assessing adherence, adverse events (aiming for no severe and minimal), acceptability and suitability of outcome measures. Results Recruitment proved to be challenging and despite targeting 230 participants directly through support groups, and many more through social media, nine families (of the planned 10) signed up for the trial. The completion rate for the study was excellent at 100%. Exploration of secondary aims revealed that (1) adherence to each aspect of the dietary protocol was very good; (2) two mild adverse events were reported; (3) parents rated the treatment as having good acceptability; (4) data collection and outcome measures were broadly feasible for use in an RCT with a few suggestions recommended; (5) descriptive data for outcome measures is presented and suggests that further exploration of gut microbiota, ADHD symptoms and sleep would be helpful in future research. Conclusions This study provides preliminary evidence for the feasibility of a microbiome-targeted dietary intervention in children with ADHD. Recruitment was challenging, but the diet itself was well-tolerated and adherence was very good. Families wishing to trial this diet may find it an acceptable intervention. However, recruitment, even for this small pilot study, was challenging. Because of the difficulty experienced recruiting participants, future randomised controlled trials may wish to adopt a simpler dietary approach which requires less parental time and engagement, in order to recruit the number of participants required to make meaningful statistical interpretations of efficacy. Trial registration ClinicalTrials.gov Identifier: NCT03737877 . Registered 13 November 2018—retrospectively registered, within 2 days of the first participant being recruited.

Objetivos: Evaluar el flujo salival en reposo y estimulado y la prevalencia de xerostomía y/ o hiposialia en mujeres posmenopáusicas, considerando la condición sistémica de cada participante. Objetivos específicos: a) estimar la correspondencia entre el relato de xerostomía y la condición de hiposialia; b) analizar la probable asociación entre xerostomía e hiposalivación con signos y/o síntomas deperiodontitis. Métodos: Es un estudio descriptivo y transversal realizado en la Clínica Integrada de la Facultad de Odontología de la Udelar. La muestra estará compuesta por 25 participantes en etapa postmenopáusica y similar tamaño en período fértil. La metodología consiste en anamnesis y sialometría de reposo y estimulada. Criterios de inclusión: sexo femenino, rango etario 45-55 años, en etapa posmenopáusica. Como grupo control se relevará población de sexo femenino en etapa fértil y rango etario 35 a 44 años. Criterios de exclusión: haber recibido profilaxis bucal profesional y/o tratamiento periodontal los últimos 6 meses. Se realiza anamnesis sobre xerostomía y de la historia clínica se obtienen los índices periodontales registrados antes del tratamiento. La obtención de saliva de reposo y estimulada sigue un protocolo. Resultados esperados: La sequedad bucal persistente es un importante problema de salud que ocasiona alteraciones funcionales y lesiones orales. Se espera que el grupo objeto de estudio presente mayor prevalencia de sequedad bucal y/o de enfermedad periodontal.

Rationale & Objective: Venglustat, a glucosylceramide synthase inhibitor, inhibits cyst growth and reduces kidney failure in mouse models of autosomal dominant polycystic kidney disease (ADPKD). STAGED-PKD aims to determine the safety and efficacy of venglustat and was designed using patient enrichment for progression to end-stage kidney disease and modeling from prior ADPKD trials. Study Design: STAGED-PKD is a 2-stage, international, double-blind, randomized, placebo-controlled trial in adults with ADPKD (Mayo Class 1C-1E) and estimated glomerular filtration rate (eGFR) 45-

La dinámica de la categoría patrimonio cultural ha dado lugar a numerosas variables conceptuales a lo largo del tiempo. Sin embargo, algunos bienes patrimoniales continúan sin identificación y reconocimiento. Este es el caso de los bienes patrimoniales agrarios, que históricamente han sido objeto de un proceso de marginación, que impacta reiteradamente en el mundo rural y sus protagonistas. Durante la última década, este vacío se ha llenado a raíz de la propuesta de constituir la categoría de Patrimonio Agrario, que permite la valoración de los bienes patrimoniales agrarios desde la premisa de que la agricultura es cultura. Más recientemente, el debate sobre este concepto y su utilización ha trascendido las fronteras europeas y ha llegado al Sur global, especialmente al territorio brasileño, donde los investigadores han estado trabajando en su aplicación. Este artículo se propone analizar las caívas, abordadas como un ejemplo de patrimonio agrario ubicado en el sur de Brasil. Con este objetivo, se utilizó un enfoque cualitativo, marcado por una amplia revisión bibliográfica sobre los temas centrales de la investigación, revisión sistemática de documentos y salidas de campo para estudios in situ de las caívas ubicadas en el corte territorial previamente definido. Entre los principales resultados obtenidos destaca la identificación de un amplio abanico de bienes patrimoniales agrarios presentes en el contexto de las caívas, cuyo mantenimiento de la actividad productiva es condición fundamental para su conservación. Se concluye que las caívas configuran efectivamente un ejemplo de patrimonio agrario y que esta categoría patrimonial tiene un potencial relevante de aplicabilidad, especialmente en territorios que buscan estrategias alternativas de desarrollo.

Abstract Background Neurological outcome and mortality of patients suffering from poor grade subarachnoid hemorrhage (SAH) may have changed over time. Several factors, including patients’ characteristics, the presence of hydrocephalus and intraparenchymal hematoma, might also contribute to this effect. The aim of this study was to assess the temporal changes in mortality and neurologic outcome in SAH patients and identify their predictors. Methods We performed a single center retrospective cohort study from 2004 to 2018. All non-traumatic SAH patients with poor grade on admission (WFNS score of 4 or 5) who remained at least 24 h in the hospital were included. Time course was analyzed into four groups according to the years of admission (2004–2007; 2008–2011; 2012–2015 and 2016–2018). Results A total of 353 patients were included in this study: 202 patients died (57 %) and 260 (74 %) had unfavorable neurological outcome (UO) at 3 months. Mortality tended to decrease in in 2008–2011 and 2016–2018 periods (HR 0.55 [0.34–0.89] and HR 0.33 [0.20–0.53], respectively, when compared to 2004–2007). The proportion of patients with UO remained high and did not vary significantly over time. Patients with WFNS 5 had higher mortality (68 % vs. 34 %, p = 0.001) and more frequent UO (83 % vs. 54 %, p = 0.001) than those with WFNS 4. In the multivariable analysis, WFNS 5 was independently associated with mortality (HR 2.12 [1.43–3.14]) and UO (OR 3.23 [1.67–6.25]). The presence of hydrocephalus was associated with a lower risk of mortality (HR 0.60 [0.43–0.84]). Conclusions Both hospital mortality and UO remained high in poor grade SAH patients. Patients with WFNS 5 on admission had worse prognosis than others; this should be taken into consideration for future clinical studies.

We present the development and characterization of a nasal drug delivery system comprised of a thermosensitive mucoadhesive hydrogel based on a mixture of the polymers Poloxamer 407, Poloxamer 188 and Hydroxypropyl-methylcellulose, and the psychedelic drug 5-methoxy-N,-N-dimethyltryptamine. The development relied on a 3 × 3 Box-Behnken experimental design, focusing on optimizing gelification temperature, viscosity and mucoadhesion. The primary objective of this work was to tailor the formulation for efficient nasal drug delivery. This would increase contact time between the hydrogel and the mucosa while preserving normal ciliary functioning. Following optimization, the final formulation underwent characterization through an examination of the in vitro drug release profile via dialysis under sink conditions. Additionally, homogeneity of its composition was assessed using Raman Confocal Spectroscopy. The results demonstrate complete mixing of drug and polymers within the hydrogel matrix. Furthermore, the formulation exhibits sustained release profile, with 73.76% of the drug being delivered after 5 h in vitro. This will enable future studies to assess the possibility of using this formulation to treat certain mental disorders. We have successfully developed a promising thermosensitive and mucoadhesive hydrogel with a gelling temperature of around 32 °C, a viscosity close to 100 mPas and a mucoadhesion of nearly 4.20 N·m. [ABSTRACT FROM AUTHOR]

Abstract Intravenous fluid administration should be considered as any other pharmacological prescription. There are three main indications: resuscitation, replacement, and maintenance. Moreover, the impact of fluid administration as drug diluent or to preserve catheter patency, i.e., fluid creep, should also be considered. As for antibiotics, intravenous fluid administration should follow the four Ds: drug, dosing, duration, de-escalation. Among crystalloids, balanced solutions limit acid–base alterations and chloride load and should be preferred, as this likely prevents renal dysfunction. Among colloids, albumin, the only available natural colloid, may have beneficial effects. The last decade has seen growing interest in the potential harms related to fluid overloading. In the perioperative setting, appropriate fluid management that maintains adequate organ perfusion while limiting fluid administration should represent the standard of care. Protocols including a restrictive continuous fluid administration alongside bolus administration to achieve hemodynamic targets have been proposed. A similar approach should be considered also for critically ill patients, in whom increased endothelial permeability makes this strategy more relevant. Active de-escalation protocols may be necessary in a later phase. The R.O.S.E. conceptual model (Resuscitation, Optimization, Stabilization, Evacuation) summarizes accurately a dynamic approach to fluid therapy, maximizing benefits and minimizing harms. Even in specific categories of critically ill patients, i.e., with trauma or burns, fluid therapy should be carefully applied, considering the importance of their specific aims; maintaining peripheral oxygen delivery, while avoiding the consequences of fluid overload.

O objetivo do presente estudo foi coletar os níveis de lactato em Cadetes atletas de Pentatlo Militar, antes e imediatamente após a execução da Pista de Obstáculos. Compuseram a amostra desta pesquisa 6 (seis) atletas do sexo masculino e 4 (quatro) atletas do sexo feminino, todos saudáveis, ativos e praticantes da modalidade de pentatlo militar, Cadetes da AMAN e idade de 22 ± 2,8 anos. O lactímetro utilizado foi o Accutrend® Plus e as lancetas da marca G-tech, todas descartáveis. Os valores de lactato apresentados por ambos os grupos foram extremamente elevados, sendo que o valor médio antes da competição dos homens foi 65% maior que o das mulheres e o valor anterior à competição dos homens foi 24,5% maior que o das mulheres. A média do lactato produzido pelos homens, antes da execução da PPM, foi de 4,01 ±1,49 Mmol/L de sangue, enquanto a média das mulheres foi de 2,48 ±0,42 Mmol/L de sangue. A média de lactato coletado após a execução da PPM foi de 17,36 Mmol/L de sangue para os homens e 13,95 Mmol/L de sangue para as mulheres. Se compararmos o nível de lactato produzido na PPM, com o que existe vigente na literatura, podemos afirmar que o estresse fisiológico apresentado atingiu valores de referência extremamente elevados.

Chagas disease is caused by the protozoan Trypanosoma cruzi (T. cruzi). It remains the major parasitic disease in Latin America and is spreading worldwide, affecting over 10 million people. Hundreds of new compounds with trypanosomicidal action have been identified from different sources such as synthetic or natural molecules, but they have been deficient in several stages of drug development (toxicology, scaling-up, and pharmacokinetics). Previously, we described a series of compounds with simple structures, low cost, and environmentally friendly production with potent trypanosomicidal activity in vitro and in vivo. These molecules are from three different families: thiazolidenehydrazines, diarylideneketones, and steroids. From this collection, we explored their capacity to inhibit the triosephosphate isomerase and cruzipain of T. cruzi. Then, the mechanism of action was explored using NMR metabolomics and computational molecular dynamics. Moreover, the mechanism of death was studied by flow cytometry. Consequently, five compounds, 314, 793, 1018, 1019, and 1260, were pre-clinically studied and their pharmacologic profiles indicated low unspecific toxicity. Interestingly, synergetic effects of diarylideneketones 793 plus 1018 and 793 plus 1019 were evidenced in vitro and in vivo. In vivo, the combination of compounds 793 plus 1018 induced a reduction of more than 90% of the peak of parasitemia in the acute murine model of Chagas disease.

Background: General pathophysiological mechanisms regarding associations between fluid administration and intra-abdominal hypertension (IAH) are evident, but specific effects of type, amount, and timing of fluids are less clear. Objectives: This review aims to summarize current knowledge on associations between fluid administration and intra-abdominal pressure (IAP) and fluid management in patients at risk of intra-abdominal hypertension and abdominal compartment syndrome (ACS). Methods: We performed a structured literature search from 1950 until May 2021 to identify evidence of associations between fluid management and intra-abdominal pressure not limited to any specific study or patient population. Findings were summarized based on the following information: general concepts of fluid management, physiology of fluid movement in patients with intra-abdominal hypertension, and data on associations between fluid administration and IAH. Results: We identified three randomized controlled trials (RCTs), 38 prospective observational studies, 29 retrospective studies, 18 case reports in adults, two observational studies and 10 case reports in children, and three animal studies that addressed associations between fluid administration and IAH. Associations between fluid resuscitation and IAH were confirmed in most studies. Fluid resuscitation contributes to the development of IAH. However, patients with IAH receive more fluids to manage the effect of IAH on other organ systems, thereby causing a vicious cycle. Timing and approach to de-resuscitation are of utmost importance, but clear indicators to guide this decision-making process are lacking. In selected cases, only surgical decompression of the abdomen can stop deterioration and prevent further morbidity and mortality. Conclusions: Current evidence confirms an association between fluid resuscitation and secondary IAH, but optimal fluid management strategies for patients with IAH remain controversial.

We study the problem of learning good heuristic functions for classical planning tasks with neural networks based on samples represented by states with their cost-to-goal estimates. The heuristic function is learned for a state space and goal condition with the number of samples limited to a fraction of the size of the state space, and must generalize well for all states of the state space with the same goal condition. Our main goal is to better understand the influence of sample generation strategies on the performance of a greedy best-first heuristic search (GBFS) guided by a learned heuristic function. In a set of controlled experiments, we find that two main factors determine the quality of the learned heuristic: the algorithm used to generate the sample set and how close the sample estimates to the perfect cost-to-goal are. These two factors are dependent: having perfect cost-to-goal estimates is insufficient if the samples are not well distributed across the state space. We also study other effects, such as adding samples with high-value estimates. Based on our findings, we propose practical strategies to improve the quality of learned heuristics: three strategies that aim to generate more representative states and two strategies that improve the cost-to-goal estimates. Our practical strategies result in a learned heuristic that, when guiding a GBFS algorithm, increases by more than 30% the mean coverage compared to a baseline learned heuristic. [ABSTRACT FROM AUTHOR]

Despite the growing literature on interdisciplinary teaching experiences in higher education, setting an interdisciplinary course remains an intuitive process of problematic transmission among teachers. We defined an interdisciplinary course structure grounded in constructivism, academic motivation, and social and managing psychology. The teaching strategy included teamwork, problem-based learning (PBL), and activities to fostering academic motivation and working with diverse perspectives. Six interdisciplinary teaching teams developed courses for undergraduate students from multiple university areas. The student course experience questionnaire and student reflective writing pieces were used as instruments for data collection, and a mixed-methods approach was used for data analysis. From the student perspective, participating in an interdisciplinary course influenced the development of four top skills and attitudes: to work as a team member, to explore ideas confidently with other people, to develop as a person, and to develop relevant, ethical, social, and professional perspectives. Impact was also found in developing enthusiasm for learning, tackling unfamiliar problems, and becoming an active enquiring learner. Results indicated course characteristics linked to five academic motivation areas, pointing to 'success' and 'caring' experiences as the most influential. Also, teamwork was a central aspect of the experience, positively influenced by group diversity and the development of a learning community. In summary, this work offers insights into interdisciplinary course development and evaluation, guiding teachers to focus on aspects rarely attended in traditional higher education courses.

This review aims at presenting an overview on metformin effects in diabetic and pre-diabetic states as well as in Polycystic Ovary Syndrome. The molecular mechanisms in which metformin is involved are discussed in depth. Particular attention is paid to the metabolic alterations and infertility which are important aspects characterizing PCOS. The part devoted to the molecular mechanisms underlying the metformin activity is a necessary introduction to the following sections and helps explaining its therapeutic activity in disorders where the common denominator is insulin resistance. The review also compares the effects of metformin with those of other therapeutic molecules. An important part is also dedicated to the side effects and limitations in the use of this drug, with a particular attention to the long-term effects. Metformin exerts multiple activities at the molecular level, still partly to be clarified, and induces a number of side effects. For these reasons, it should be administered with caution and always under careful control to patients suffering from diabetic and pre-diabetic states, and from PCOS. Furthermore, wherever possible it would be necessary to prefer the use of safer molecules.

D-chiro-inositol is one of the nine stereoisomers of inositol, a water-soluble cyclic carbohydrate with six hydroxyl groups. Inositol has an essential function in the activation of crucial enzymes in glucose metabolism. In fact, D-chiro-inositol shortage can lead to insulin resistance development. D-chiro-inositol administration in pathologies where insulin resistance is an important factor, i.e. diabetes, has given satisfying results; however, in other disorders, i.e. Polycystic ovary syndrome, this stereoisomer can be detrimental for pregnancy. Indeed, high follicular D-chiro-inositol levels in the presence of reduced myo-inositol values are associated with worsened oocyte quality. In conclusion, some recent studies and researches suggest that restoring the physiologic ratio between myo-inositol and D-chiro-inositol is mandatory to protect the efficiency of the reproductive system in women.

Objective: To compare bioelectrical impedance analysis (BIA)-derived parameters in healthy volunteers and critically ill patients and to assess its prognostic value in an ICU patient cohort. Design: Retrospective, observational data analysis. Setting: Single centre, tertiary-level ICU (Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg Hospital). Patients: 101 patients and 101 healthy subjects, participants of International Fluid Academy Days. Measurements and main results: Compared to healthy volunteers, both male and female ICU patients had significantly higher values for total body water (TBW), extracellular water (ECW), extracellular fluid (ECF), plasma, and interstitial fluid volumes. The phase angle was significantly lower and the malnutrition index was significantly higher in ICU patients, regardless of gender. Non-survivors in the ICU had significantly higher extracellular water content (ECW, 50.7 ± 5.1 vs. 48.9 ± 4.3%, p = 0.047) and accordingly significantly lower intracellular water (ICW, 49.2 ± 5.1 vs. 51.1 ± 4.3%, p = 0.047). The malnutrition index was also significantly higher in non-survivors compared to survivors (0.94 ± 0.17 vs. 0.87 ± 0.16, p = 0.048), as was the capillary leak index (ECW/ICW). Conclusions: Compared to healthy volunteers, this study observed a higher malnutrition index and TBW in ICU patients with an accumulation of fluids in the extracellular compartment. ICU non-survivors showed similar results, indicating that ICU patients and a fortiori non-survivors are generally overhydrated, with increased TBW and ECW, and more undernourished, as indicated by a higher malnutrition index. [ABSTRACT FROM AUTHOR]

Abstract Introduction The use of intracanal medications with antimicrobial properties is essential for decontaminating root canals during endodontic treatment. Calcium hydroxide is used for this because of its excellent properties. Melaleuca alternifolia oil has shown medicinal importance by demonstrating antifungal and bactericidal action against proven human pathogens. Objective To evaluate the physical and chemical aspects such as pH and calcium release, of Melaleuca alternifolia oil associated with calcium hydroxide, during different time intervals. Material and method Calcium hydroxide powder was added to vehicles to reach a concentration of 72mg / 0.1mL. Three groups were formed: Group I: Calcium Hydroxide + Distilled Water; Group II: Calcium hydroxide + Propylene Glycol; Group III: Calcium hydroxide + Melaleuca oil. The pH of each group was measured after time intervals of 10 minutes; 24 and 48 hours; 7, 15 and 30 days after tooling by a pH meter. Calcium release was analyzed by atomic absorption spectrometry equipped with a calcium hollow cathode lamp. Data were statistically analyzed by using the Kruskall-Wallis and Dunn test. Result Group II showed high pH, similar to group III that remained uniform at 15 and 30 days. Calcium release that began after 24 hours, was similar in Groups II and III, and showed a peak release in 48 hours. Conclusion The association of Melaleuca oil with calcium hydroxide showed good results in the pH and calcium release analyses, and showed action similar to that of propylene glycol + calcium hydroxide.