Preparation and Characterization of a Rifampicin Coamorphous Material with Tromethamine Coformer: An Experimental-Theoretical Study.

Rifampicin (RIF) is an antibiotic used to treat tuberculosis and leprosy. Even though RIF is a market-available drug, it has a low aqueous solubility, hindering its bioavailability. Among the strategies for bioavailability improvement of poorly soluble drugs, coamorphous systems have been revealed as an alternative in the increase of the aqueous solubility of drug systems and at the same time also increasing the amorphous state stability and dissolution rate when compared with the neat drug. In this work, a new coamorphous form from RIF and tromethamine (TRIS) was synthesized by slow evaporation. Structural, electronic, and thermodynamic properties and solvation effects, as well as drug-coformer intermolecular interactions, were studied through density functional theory (DFT) calculations. Powder X-ray diffraction (PXRD) data allowed us to verify the formation of a new coamorphous. In addition, the DFT study indicates a possible intermolecular interaction by hydrogen bonds between the available amino and carbonyl groups of RIF and the hydroxyl and amino groups of TRIS. The theoretical spectra obtained are in good agreement with the experimental data, suggesting the main interactions occurring in the formation of the coamorphous system. PXRD was used to study the physical stability of the coamorphous system under accelerated ICH conditions (40 °C and 75% RH), indicating that the material remained in an amorphous state up to 180 days. The thermogravimetry result of this material showed a good thermal stability up to 153 °C, and differential scanning calorimetry showed that the glass temperature (Tg) was at 70.0 °C. Solubility studies demonstrated an increase in the solubility of RIF by 5.5-fold when compared with its crystalline counterpart. Therefore, this new material presents critical parameters that can be considered in the development of new coamorphous formulations.

New polymorphic phase of arachidic acid crystal: structure, intermolecular interactions, low-temperature stability and Raman spectroscopy combined with DFT calculations.

Saturated monocarboxylic fatty acids with long carbon chains are organic compounds widely used in several applied fields, such as energy production, thermal energy storage, antibactericidal, antimicrobial, among others. In this research, a new polymorphic phase of arachidic acid (AA) crystal was synthesized and its structural and vibrational properties were studied by single-crystal X-ray diffraction (XRD) and polarized Raman scattering. The new structure of AA was solved at two different temperature conditions (100 and 300 K). XRD analysis indicated that this polymorph belongs to the monoclinic space group P21/c (C2h5), with four molecules per unit cell (Z = 4). All molecules in the crystal lattice adopt a gauche configuration, exhibiting a R22(8) hydrogen bond pattern. Consequently, this new polymorphic phase, labeled as B form, is a polytype belonging to the monoclinic symmetry, i.e., Bm form. Complementarily, Hirshfeld's surfaces were employed to analyze the intermolecular interactions within the crystal lattice of this polymorph at temperatures of 100 and 300 K. Additionally, density functional theory (DFT) calculations were performed to assign all intramolecular vibration modes related to experimental Raman-active bands, which were properly calculated using a dimer model, considering a pair of AA molecules in the gauche configuration, according to the solved-crystal structure.

Predictive factors of surgery in metastatic colorectal cancer: a retrospective cohort study.

INTRODUCTION: Current management of metastatic colorectal cancer is based on neoadjuvant chemotherapy. Few studies have reported on surgery procedures in patients with metastatic colorectal cancer. The objective of this study was to describe our institutional experience with emergency surgery performed in patients with metastatic colorectal cancer during chemotherapy. PATIENTS AND METHODS: This was a retrospective cohort study including adult patients of ≤80 years with a metastatic colorectal cancer between 2017 and 2020 and undergoing surgery during chemotherapy. Statistical analyses were based on Kaplan-Meier's curve and Cox proportional hazard model. The surgery statistical risk during chemotherapy was studied through all tumor and patient's characteristics. Multivariable logistic regression models were used to identify predictive factors of emergency surgery in these patients. RESULTS: Seventy-two cases were identified and 60% patients undergone an emergency surgery. By Kaplan-Meier's analyses, intestinal surgery was much more frequent and early in patients who have severe stenosis (either blocking or only permeable using a gastroscope) at the time of diagnosis. Patients with severe malignant stenosis presented a 6.28 time higher surgery risk (p < .0001). The median time between admission and surgery was 54 days in patients with severe stenosis who were operated. CONCLUSION: The degree of colorectal tumor stenosis measured by endoscopy was a risk factor for emergency surgery in patients with metastatic colorectal cancer during neoadjuvant chemotherapy. In this group of patients presenting low survival outcomes, further studies are needed to define the place of preventive surgery, avoiding emergency surgery and morbidity in such fragile patients.

Development of nanostructured formulation from naringenin and silk fibroin and application for inhibition of lipoxygenase (LOX).

A simple low-energy method was used to obtain polymeric nanoparticles containing silk fibroin (SF), fatty butyl esters (oily phase) and the flavonoid naringenin. Experimental planning (Box-Behnken) was applied to investigate the optimal conditions for three factors (variation of the concentrations of SF, naringenin and fatty butyl ester) at three levels, with evaluation of particle size, polydispersity index (PDI) and zeta potential (ZP) as responses. The results showed that the polymeric particle was formed with sizes of 179.6 to 633.9 nm, PDI of 0.33 to 0.77 and ZP of -60.4 to -38.8 mV. The best responses under the optimized conditions (Nari-SF 9 and 15) were characterized through transmission electron microscopy (TEM), Fourier-transform infrared (FT-IR), visible ultraviolet (UV-vis) and fluorescence, which confirmed that coated nanoparticles had been obtained. It was shown that the nanoformulation had excellent stability, the bioavailability of naringenin had been improved through use of the biopolymer and high inhibition of the enzyme lipoxygenase had been achieved in vitro.

Pediatric inferior turbinate surgery: A review and meta-analysis of midterm nasal patency.

OBJECTIVES: The surgical treatment of children with enlarged inferior turbinates is still controversial. Foundational evidence for indicating turbinoplasty is still scarce, and there is a myriad of proposed techniques. This work aimed to address the midterm nasal obstruction outcomes of pediatric inferior turbinate surgery. MATERIAL AND METHODS: A Literature search across PUBMED and Cochrane collaboration databases was undertaken, using the MeSH terms: turbinates, nasal obstruction, surgery, and children. Articles focusing on turbinate surgery with an exclusively pediatric cohort were included. The minimum follow-up time for inclusion was set at four months, and only the latest available follow-up in each study was considered. All the integrated studies used objective instruments to quantify nasal obstruction before and after surgery. A comprehensive review and meta-analysis were performed to assess nasal outcomes after the intervention. The 95% confidence interval of the effect magnitude for each study was calculated to elucidate effect sizes. RESULTS: Seven studies met the inclusion criteria for review, and five were included in the meta-analysis, accounting for a total of 510 patients. The follow-up period ranged from 4 months to 1 year. Pooled results showed that nasal patency was significantly improved after surgery (p < 0.001) in the midterm follow-up. No significant differences were found between bone-sparing and bone-removal procedures (p = 0.38). CONCLUSION: This is the first meta-analysis to address midterm results of pediatric turbinate surgery. Our results suggest a positive impact of inferior turbinate surgery on nasal patency, irrespective of technique.

Laryngectomy: Phonation Alternatives and Their Impact on the Quality of Life.

Background The decision to consent to surgery is a life-changing moment. This study addresses the impact of total laryngectomy (TL) on phonation and its effect on the quality of life (QoL) of patients. The primary objective of this cohort study is to compare the alternatives in phonation rehabilitation, and the secondary objective is to identify concurrent predictors of vocal outcomes. Methodology To perform a comprehensive analysis, we reviewed data from patients who underwent TL with bilateral radical neck dissection in the Department of Otolaryngology, Head and Neck Surgery at Centro Hospitalar Universitário de Santo António between January 2010 and October 2022. Adult patients who consented to participate in the study and underwent subjective evaluation were included in this study. Data regarding clinical history was primarily collected. Statistical analysis was performed using SPSS version 26 (IBM Corp., Armonk, NY, USA). Different types of vocal rehabilitation formed the subgroups to be compared. An additional analysis was performed for baseline variables collected in the clinical records, and vocal outcomes were measured using the Self-Evaluation of Communication Experiences After Laryngectomy (SECEL) questionnaire. Furthermore, linear models taking SECEL scores as the outcome were developed. Results The first search identified a total of 124 patients operated during the study period. In total, 63 patients were alive at the time of the current follow-up, with 61 deaths (49%). Overall, 26 of the 63 alive patients completed the SECEL questionnaire. All patients were male. The mean age at diagnosis was 62.2 ± 10.6 years. The mean age at the time of subjective vocal assessment with the SECEL questionnaire was 66.3 ± 10.4 years. The mean time of follow-up after the initial diagnosis was 4 ± 3.8 years. A statistically significant difference was observed in esophageal speech (ES), which was inferior to other modalities (mean SECEL total score for ES: 46.6 ± 12.2 vs. mean SECEL total score for all other modalities: 33 ± 15.1; p = 0.03). The follow-up time correlated significantly with vocal function, as measured by the SECEL questionnaire (p = 0.013). Conclusions The SECEL questionnaire can be a valuable tool to evaluate QoL in laryngectomy patients, given its usefulness in assessing the psychological impact derived from vocal functionality in this group. ES appears inferior to other modalities regarding voice-related QoL.

Impact of adenotonsillectomy in pediatric respiratory function / Impacto de la cirugía adenoamigdalar sobre la función respiratoria pediátrica

Introduction: Adenotonsillar hypertrophy (ATH) is an important health condition that leads to upper airway obstruction and constitutes the main cause of obstructive sleep disordered breathing (OSDB) in children. The aim of this study was to analyze the effect of surgical intervention on spirometrical parameters of children with ATH/OSDB and upper airway recurrent infections (URTIs). Material and methods The study covered children treated surgically in a Pediatric Ambulatory Unit in a tertiary hospital. Spirometric tests were performed before and three months after surgery and results were compared. Results A total of 78 children were enrolled with a mean age of 6.95 ± 2,81 years. There was a significant improvement in forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak expiratory flow (PEF) and forced expiratory flow rate at 25% (F25) values after surgery in children suffering from OSDB (FVC pre: 1.52 ± 0.47 L vs FVC post: 1.85 ± 0.63 L, p < 0.001; FEV1 pre: 1.24 ± 0.38 L vs FEV1 post: 1.39 ± 0.40 L, p = 0.014; PEF pre: 2.04 ± 0.85 L/s vs PEF post: 2.33 ± 0.76 L/s, p = 0.014; F25 pre: 1.77 ± 0.77 L/s vs F25 post: 2.02 ± 0.73 L/s, p = 0.030). On a multivariate analysis model, preoperative tonsil size and performing tonsillectomy were the most significant determinants of improvement in spirometric values (p < 0.05). Children with isolated adenoid hypertrophy without tonsillar obstruction and those with URTIs alone did not show relevant differences in spirometric values after surgery (p > 0.05). No significant differences were found concerning pre-operative and post-operative forced expiratory flow rate at 75% (F75) and forced expiratory flow between 25 and 75% of the pulmonary volume (FEF25–75%) in any group (p > 0.05). Conclusions Surgery seems effective in ameliorating spirometry values in patients with OSDB and ATH, namely FVC, FEV1, PEF and F25. ... (AU)

Introducción: La hipertrofia adenoamigdalar (HAA) es una importante condición de salud que conduce a la obstrucción de las vías respiratorias superiores y constituye la principal causa de trastornos respiratorios obstructivos del sueño (TROS) en los niños. El objetivo de este estudio fue analizar el efecto de la intervención quirúrgica sobre los parámetros espirométricos de niños con HAA/TROS e infecciones recurrentes de las vías respiratorias superiores (IrVAS). Material y Métodos El estudio abarcó a niños operados en una Unidad Ambulatoria Pediátrica de un hospital de tercer nivel. Se realizaron espirometrías antes y tres meses después de la cirugía y se compararon los resultados. Resultados Se incluyeron un total de 78 niños con una edad media de 6,95 ± 2,81 años. Hubo una mejora significativa en los valores de capacidad vital forzada (FVC), volumen espiratorio forzado en el primer segundo (FEV1), flujo espiratorio máximo (PEF) y tasa de flujo espiratorio forzado al 25 % (F25) después de la cirugía en niños que sufrían de TROS (FVC pre: 1.52 ± 0.47 L vs FVC post: 1.85 ± 0.63 L, p < 0.001; FEV1 pre: 1.24 ± 0.38 L vs FEV1 post: 1.39 ± 0.40 L, p = 0.014; PEF pre: 2.04 ± 0.85 L/s vs PEF post: 2.33 ± 0.76 L/s, p = 0.014; F25 pre: 1.77 ± 0.77 L/s vs F25 post: 2.02 ± 0.73 L/s, p = 0.030). En un modelo de análisis multivariado, el tamaño preoperatorio de las amígdalas y la amigdalectomía fueron los determinantes más significativos de la mejora en los valores espirométricos (p < 0.005). Los niños con hipertrofia adenoidea aislada sin obstrucción amigdalina y aquellos con IrVAS sin TROS no mostraron diferencias relevantes en los valores espirométricos tras la cirugía (p > 0,05). ... (AU)

Modelling metabolic performance in paediatric obstructive sleep disordered breathing: A case-control study.

Paediatric obstructive sleep disordered breathing (OSDB) has a considerable impact on cardiovascular physiology, but the consequences on children's basal metabolism and response to exercise are far from being known. The objective was to propose model estimations for paediatric OSDB metabolism at rest and during exercise. A retrospective case-control analysis of data from children submitted to otorhinolaryngology surgery was performed. The heart rate (HR) was measured, while oxygen consumption (VO2 ) and energy expenditure (EE) at rest and during exercise were obtained using predictive equations. The results for the patients with OSDB were compared with controls. A total of 1256 children were included. A total of 449 (35.7%) had OSDB. The patients with OSDB showed a significantly higher resting heart rate (94.55 ± 15.061 bpm in OSDB vs. 92.41 ± 15.332 bpm in no-OSDB, p = 0.041). The children with OSDB showed a higher VO2 at rest (13.49 ± 6.02 mL min-1 kg-1 in OSDB vs. 11.55 ± 6.83 mL min-1 kg-1 in no-OSDB, p = 0.004) and a higher EE at rest (67.5 ± 30.10 cal min-1 kg-1 in OSDB vs. 57.8 + 34.15 cal min-1 kg-1 in no-OSDB, p = 0.004). At maximal exercise, patients with OSDB showed a lower VO2 max (33.25 ± 5.82 mL min-1 kg-1 in OSDB vs. 34.28 ± 6.71 in no-OSDB, p = 0.008) and a lower EE (166.3 ± 29.11 cal min-1 kg-1 in OSDB vs. 171.4 ± 33.53 cal min-1 kg-1 in no-OSDB, p = 0.008). The VO2 /EE increment with exercise (Δ VO2 and Δ EE) was lower in OSDB for all exercise intensities (p = 0.009). This model unveils the effect of paediatric OSDB on resting and exercise metabolism. Our findings support the higher basal metabolic rates, poorer fitness performance, and cardiovascular impairment found in children with OSDB.

Zein Nanoparticles Containing Arginine-Based Surfactants: Physicochemical Characterization and Effect on the Biological Properties.

Cationic surfactants carry antimicrobial activity, based on their interaction and disruption of cell membranes. Nonetheless, their intrinsic toxicity limits their applicability. To overcome this issue, a feasible strategy consists of using solid nanoparticles to improve their delivery. The zein nanoparticles were loaded with four cationic arginine-based surfactants: one single chain Nα-lauroyl-arginine (LAM) and three Gemini surfactants Nα Nω-Bis (Nα-lauroyl-arginine) α, ω-diamide) (C3(LA)2, C6(LA)2 and C9(LA)2). Blank and loaded zein nanoparticles were characterized in terms of size, polydispersity and zeta potential. Furthermore, the antimicrobial activity against bacteria and yeasts and the hemolytic activity were investigated and compared to the surfactants in a solution. Nanoparticles were found to be monodisperse, presenting a size of between 180-341 nm, a pdI of <0.2 and a positive zeta potential of between +13 and +53 mV, remaining stable over 365 days. The nanoencapsulation maintained the antimicrobial activity as unaltered, while the extensive hemolytic activity found for the surfactants in a solution was reduced drastically. Nuclear Magnetic Ressonance (NMR), molecular docking and monolayer findings indicated that zein entraps the surfactants, interfering in the surfactant-membrane interactions. Accordingly, the nanoepcasulation of arginine surfactants improved their selectivity, while the cationic charges were free to attack and destroy bacteria and fungi; the aliphatic chains were not available to disrupt the cellular membranes.

Impact of adenotonsillectomy in pediatric respiratory function.

INTRODUCTION: Adenotonsillar hypertrophy (ATH) is an important health condition that leads to upper airway obstruction and constitutes the main cause of obstructive sleep disordered breathing (OSDB) in children. The aim of this study was to analyze the effect of surgical intervention on spirometrical parameters of children with ATH/OSDB and upper airway recurrent infections (URTIs). MATERIAL AND METHODS: The study covered children treated surgically in a Pediatric Ambulatory Unit in a tertiary hospital. Spirometric tests were performed before and three months after surgery and results were compared. RESULTS: A total of 78 children were enrolled with a mean age of 6.95 ±â€¯2,81 years. There was a significant improvement in forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak expiratory flow (PEF) and forced expiratory flow rate at 25% (F25) values after surgery in children suffering from OSDB (FVC pre: 1.52 ±â€¯0.47 L vs FVC post: 1.85 ±â€¯0.63 L, p < 0.001; FEV1 pre: 1.24 ±â€¯0.38 L vs FEV1 post: 1.39 ±â€¯0.40 L, p = 0.014; PEF pre: 2.04 ±â€¯0.85 L/s vs PEF post: 2.33 ±â€¯0.76 L/s, p = 0.014; F25 pre: 1.77 ±â€¯0.77 L/s vs F25 post: 2.02 ±â€¯0.73 L/s, p = 0.030). On a multivariate analysis model, preoperative tonsil size and performing tonsillectomy were the most significant determinants of improvement in spirometric values (p < 0.05). Children with isolated adenoid hypertrophy without tonsillar obstruction and those with URTIs alone did not show relevant differences in spirometric values after surgery (p > 0.05). No significant differences were found concerning pre-operative and post-operative forced expiratory flow rate at 75% (F75) and forced expiratory flow between 25 and 75% of the pulmonary volume (FEF25-75%) in any group (p > 0.05). CONCLUSIONS: Surgery seems effective in ameliorating spirometry values in patients with OSDB and ATH, namely FVC, FEV1, PEF and F25. Spirometry may give a clue on the importance of adequate surgical resolution of pediatric lymphoid hypertrophy obstruction. No significant differences exist on spirometric parameters of children with isolated adenoid hypertrophy and URTIs without ATH. Further studies are needed in order to evaluate the potential benefit of spirometry utilization in the daily clinical setting.

Elucidating the phase transitions of decanoic-acid crystal by XRD, Raman, group theory and Gibbs energy analyses combined with DFT calculations.

This research reports a series of phase transitions in the decanoic-acid (DA) crystal under low-temperature conditions, which were elucidated by XRD, Raman scattering and DFT calculations in a dimer of DA in the C form (monoclinic structure). The first phase change was noticed within the 210-190 K interval duly characterized as a transition of second-order type, as indicated by Gibbs energy behavior, suggesting that the monoclinic structure (P21/c) of the crystal is not changed. The second change was observed nearly 110-90 K, whose transition is first-order type occurring from the C form to an A form (triclinic), possibly belonging to the P1 space group. This new polymorphic phase was duly predicted through DFT calculations. According to Gibbs energy behavior, the third phase change (∼30-10 K) is proposed to be a transition from the A form to a new polymorphic phase that probably is a first-order transition, likely associated with a change from the P1 space group to P-1. Furthermore, group theory and wavenumber vs temperature plots' analyses corroborated the phase transitions undergone by DA crystal. In addition, anharmonicity effects in several Raman bands' behavior were noticed during the cooling. A correct assignment for the Raman and IR modes via DFT calculations at room-temperature conditions is also provided herein.

Olfactory Cleft Length: A Possible Risk Factor for Persistent Post-COVID-19 Olfactory Dysfunction.

INTRODUCTION: To date, little is known about predisposing factors for persistent COVID-19-induced olfactory dysfunction (pCIOD). The objective was to determine whether olfactory cleft (OC) measurements associate with pCIOD risk. MATERIAL AND METHODS: Three subgroups were recruited: group A included patients with pCIOD, group B included patients without olfactory dysfunction following SARS-CoV-2 infection (ntCIOD), and group C consisted in controls without past history of SARS-CoV-2 infection (noCOVID-19). Olfactory perception threshold (OPT) and visual analog scale for olfactory impairment (VAS-olf) were obtained. OC measurements were obtained through computed tomography scans. Results were subsequently compared. RESULTS: A total of 55 patients with a mean age of 39 ± 10 years were included. OPT was significantly lower in pCIOD patients (group A: 4.2 ± 2.1 vs. group B: 12.3 ± 1.8 and group C: 12.2 ± 1.5, p < 0.001). VAS-olf was significantly higher in pCIOD (group A: 6 ± 2.6 vs. group B: 1.7 ± 1.6 and group C: 1.6 ± 1.5, p < 0.001). OC length was significantly higher in group A (42.8 ± 4.6) compared to group B (39.7 ± 3.4, p = 0.047) and C (39.8 ± 4, p = 0.037). The odd of pCIOD occurring after COVID-19 infection increased by 21% (95% CI [0.981, 1.495]) for a one unit (mm) increase in OC length. The odd of pCIOD occurring was 6.9 times higher when OC length >40 mm. CONCLUSION: Longer OC may be a predisposing factor for pCIOD. This study is expected to encourage further research on OC morphology and its impact on olfactory disorders.

Physicochemical properties calculated using DFT method and changes of 5-methyluridine hemihydrate crystals at high temperatures.

5-methyluridine hemihydrate (5 mU) single crystals were synthesized by the slow solvent evaporation method. The physicochemical properties, such as frontier molecular orbitals, global reactivity indices and vibrational were computationally studied through density functional theory (DFT). In addition, structural, vibrational, and thermal properties were obtained by powder X-ray diffraction (PXRD), Raman spectroscopy, thermogravimetric (TG) analysis and differential scanning calorimetry (DSC). PXRD evaluated the structural behavior of 5 mU crystal in the temperature range of 300-460 K. The high-temperature PXRD results suggested that the crystal undergoes two dehydration processes, being a first occurring from the orthorhombic structure (P21212) to triclinic (P1), in which the water losses occurred around 380 K. A second dehydration triggers the change from the triclinic structure to monoclinic (P21) within the 420-435 K temperature range. Furthermore, after this temperature, the anhydrous 5 mU suffers a melting process near 460 K, which is remarkably characterized as an irreversible process. Raman spectroscopy was carried out to identify the vibrational modes linked to the water molecule and the noticeable changes in these bands due to high-temperature effects around 380 K and 410 K. Indeed, changes on Raman bands, such as intensity inversion, the disappearance of bands associated with the hydrogen bonds formed from the water molecules and uracil group, and the ribose group were observed. Finally, this study provided details on the structural and vibrational changes caused by the dehydration of 5 mU crystals and the importance of hydrogen bonds for understanding the intermolecular interactions of the 5 mU, a methylated nucleoside with important biological functions.

PM10 Alters Trophoblast Cell Function and Modulates miR-125b-5p Expression.

Air pollution is one of the largest global environmental health hazards that threaten premature mortality or morbidity. Particulate matter 10 (PM10) has been demonstrated to contribute to several human diseases via dysregulated miRNA expression. Trophoblast cells play a key role in implantation and placentation for a successful pregnancy. Nonetheless, the PM10 associated trophoblast cell functions during pregnancy and miRNA expression are still unknown. Our study showed that PM10 affected HTR-8/SVneo cell viability and also decreased cell proliferation, migration, and invasion. A high concentration of PM10 caused an increase in HTR-8/SVneo cell apoptosis. Treatment with PM10 induced inflammation through the upregulated IL-1ß, IL-6, and TNF-α expression in trophoblast cells. In PM10-treated HTR-8/SVneo cells, miR-125b-5p expression was considerably increased and TXNRD1 was found to be negatively related to miR-125b-5p. Collectively, our findings revealed that PM10 could alter miR-125b-5p expression by targeting TXNRD1 and suppressing trophoblast cell functions. Additional investigations relating to the function of miR-125b-5p and its target on particulate pollution exposure in trophoblast are warranted for future biomarker or effective therapeutic approaches.

Cellulase production by Aspergillus niger using urban lignocellulosic waste as substrate: Evaluation of different cultivation strategies.

Cellulases are used in various industries, acting efficiently and sustainably in the degradation of cellulose contained in different raw materials and recovering high value products. It is the third largest group of enzymes consumed industrially, as they are required in processes linked to the food, biofuel, textile, cleaning products, among others. However, the main disadvantage in the use of commercial cellulases is the high cost. In this context, the objective of this work was to determine conditions for obtaining more efficient and economical cellulases. For this, the efficiency in obtaining the extracellular cellulases endoglucanase (CMCase) and exoglucanase (FPase) by a fungus Aspergillus niger was investigated using an urban lignocellulosic waste as substrate characterized by tree leaves collected from squares and avenues in urban areas. As urban lignocellulosic waste is an innovative raw material, its chemical composition was determined. This substrate contains 20.36% cellulose and induced the production of cellulases in all fermentation methods, proving to be a promising and sustainable source. The influence of the nutrient medium on CMCase and FPase activities was evaluated for three different sequential fermentation (SF) configurations. Medium 2 provided an increase of up to 100 U/L of CMCase and FPase in relation to medium 1. The interactive effect of pH and moisture content on CMCase e FPase production under SF was studied in a central composite design (CCD). Also, different fermentation methods (solid state, submerged and sequential) were evaluated. The use of SF increased the enzymatic activities of both cellulases by 140% compared to other conventional methods and also stood out in the production of proteins (270.05 µg/mL) and reducing sugars (1.19 mg/mL). The desirability function determined the optimal activities of CMCase and FPase as 413.49 U/L and 230.68 U/L, respectively, obtained from the optimal variables of pH 5.5 and 75% moisture content under SF. The effect of pH and moisture content on the activity of each cellulase was analyzed using the Pareto chart and response surface methodology (RSM). These results revealed favorable strategies for cellulase production, such as the use of urban lignocellulosic waste, SF and ideal operational conditions.

Structural, thermal, vibrational, solubility and DFT studies of a tolbutamide co-amorphous drug delivery system for treatment of diabetes.

Among the strategies for bioavailability improvement of poorly soluble drugs, co-amorphous systems have revealed to have a significant impact in the increase of the aqueous solubility of the drug, and at the same time increasing the amorphous state stability and dissolution rate when compared with the neat drug. Tolbutamide (TBM) is an oral hypoglycemic drug largely used in the treatment of type II Mellitus diabetes. TBM is a class II drug according to the Biopharmaceutical Classification System, meaning that it has low solubility and higher permeability. The aim of this study was to synthesize a co-amorphous material of tolbutamide (TBM) with tromethamine (TRIS). Density functional theory (DFT), allowed to study the structural, electronic, and thermodynamic properties, as well as solvation effects. In same theory level, several interactions tests were performed to obtain the most thermodynamically favorable drug-coformer intermolecular interactions. The vibrational spectra (mid infrared and Raman spectroscopy) are in accordance with the theoretical studies, showing that the main molecular interactions are due to the carbonyl, sulfonyl, and amide groups of TMB and the alcohol and amine groups of TRIS. X-ray powder diffraction was used to study the physical stability in dry condition at 25 °C of the co-amorphous system, indicating that the material remained in an amorphous state up to 90 days. Differential scanning calorimetry and thermogravimetric results showed a high increase of the Tg when compared with the amorphous neat drug, from 4.3 °C to 83.7 °C, which generally translated into good physical stability. Solubility studies demonstrated an increase in the solubility of TBM by 2.5 fold when compared with its crystalline counterpart.

Let Us Not Forget About Bleeding: A Case Report and Brief Literature Review on Hemorrhagic Vestibular Schwannoma.

Hemorrhagic vestibular schwannoma (HVS) consisting of acute intratumoral and subarachnoid hemorrhage is a rare phenomenon. We present the case of a 31-year-old woman who attended the Otorhinolaryngology department with right-sided intense tinnitus, dizziness, imbalance, and headache. Brain computed tomography revealed a spontaneous hyperdensity in the posterior fossa with marked deformation of the brainstem, middle cerebral peduncle, and cerebellum, with the near collapse of the fourth ventricle. Ophthalmology evaluation confirmed bilateral papilledema. Brain magnetic resonance imaging confirmed a voluminous 33 x 28 x 29 mm extra-axial lesion centered on the right pontine-cerebellar angle cistern, extending from the plane of the trigeminal nerve/tent of the cerebellum. The acoustic pore was enlarged. The patient underwent retrosigmoid craniotomy and microscopic tumor resection showing significant improvement in the follow-up. Pathological findings confirmed HVS. Delayed treatment of HVS can increase morbidity or even be fatal. The objective of this work is to describe and revise HVS, in order to bring awareness to this uncommon entity.

Instrumento para medir a intenção de reduzir o consumo de sal em pessoas com insuficiência cardíaca / Instrumento para medir la intención de reducir el consumo de sal en personas con insuficiencia cardíaca / Instrument for evaluating the intention to reduce salt consumption in people with heart failure

Objetivo: construir e validar instrumento para medir a intenção comportamental de reduzir o consumo de sal na dieta em pessoas com insuficiência cardíaca. Materiais e métodos: estudo metodológico, fundamentado na Theory of Planned Behavior, desenvolvido em três etapas: construção do instrumento, validação de conteúdo com juízes especialistas e validaçãosemântica com 30 pessoas da população- alvo, de março a setembro de 2018, no município de João Pessoa, Brasil. Resultados: participaram da validação de conteúdo seis juízes especialistas. O instrumento conta com 30 itens distribuídos nos construtos atitude, norma subjetiva e controle comportamental percebido. O índice de validade de conteúdo mostrouse satisfatório (≥ 80 %). Na validação semântica, o instrumento foi considerado claro e compreensível. Conclusões: como produto, dispõe-se de instrumento válido quanto ao seu conteúdo e compreensão, podendo ser aplicado em estudo-piloto para avaliar sua qualidade psicométrica em medir o comportamento de interesse no contexto da insuficiência cardíaca.

Objetivo: construir y validar un instrumento para medir la intención de reducir el consumo de sal por parte de personas con insuficiencia cardíaca. Materiales y métodos: estudio metodológico basado en la teoría del comportamiento planeado, el cual se desarrolló en tres etapas: construcción del instrumento, validación de contenido por juicio de expertos y validación semántica con 30 personas de la población objetivo, entre marzo y septiembre de 2018, en el municipio de João Pessoa, Brasil. Resultados: seis jueces expertos participaron en la validación de contenido. El instrumento consta de 30 ítems distribuidos en los constructos actitud, norma subjetiva y control conductual percibido. El índice de validez de contenido fue satisfactorio (≥ 80 %). Tras la validación semántica, el instrumento fue considerado claro y comprensible. Conclusiones: como producto, existe un instrumento válido en cuanto a contenido y comprensión, el cual puede ser aplicado en un estudio piloto para evaluar su calidad psicométrica en la medición de la conducta de interés en el contexto de la insuficiencia cardíaca.

Objective: To build and validate an instrument to measure the behavioral intention to reduce the consumption of dietary salt in people with heart failure. Materials and methods: Methodological study based on the theory of planned behavior and developed in three stages: construction of the instrument, content validation with expert judges, and semantic validation with 30 people from the target population, from March to September 2018, in the municipality of João Pessoa, Brazil. Results: Six expert judges participated in content validation. The instrument has 30 items distributed in the constructs attitude, subjective norm, and perceived behavioral control. The content validity index was satisfactory (≥ 80 %), and the semantic validation of the instrument was considered clear and understandable. Conclusions: As a product, the instrument proved to be valid in terms of content and understanding. This tool can be applied in a pilot study to assess its psychometric quality for measuring the behavior of interest in the context of heart failure.

Potential risk of BPA and phthalates in commercial water bottles: a minireview.

The global water bottling market grows annually. Today, to ensure consumer safety, it is important to verify the possible migration of compounds from bottles into the water contained in them. Potential health risks due to the prevalence of bisphenol A (BPA) and phthalates (PAEs) exposure through water bottle consumption have become an important issue. BPA, benzyl butyl phthalate (BBP), di-n-butyl phthalate (DBP) and di (2-ethylhexyl) phthalate (DEHP) can cause adverse effects on human health. Papers of literature published in English, with BPA, BBP, DBP and DEHP detections during 2017, by 2019 by liquid chromatography and gas chromatography analysis methods were searched. The highest concentrations of BPA, BBP, DBP and DEHP in all the bottled waters studied were found to be 5.7, 12.11, 82.8 and 64.0 µg/L, respectively. DBP was the most compound detected and the main contributor by bottled water consumption with 23.7% of the Tolerable Daily Intake (TDI). Based on the risk assessment, BPA, BBP, DBP and DEHP in commercial water bottles do not pose a serious concern for humans. The average estrogen equivalent level revealed that BPA, BBP, DBP and DEHP in bottled waters may induce adverse estrogenic effects on human health.

Chondroprotective effect of melatonin and strontium ranelate in animal model of osteoarthritis.

PURPOSE: To analyze the action of strontium ranelate (SR) and melatonin in isolation or in association in knees, liver and kidneys of rats Wistar with induced osteoarthritis (OA). METHODS: Thirty male rats were induced to OA through an anterior cruciate ligament transection (ACLT), and treated with melatonin and SR in isolation or in association. Morphological, histopathological, histochemical and morphometric analysis were realized of the structure of the articular capsule, as well as histopathological analysis of liver and kidneys from the animals. RESULTS: The experimental model was successful. The association of the drugs presented chondroprotective pharmacodynamics. However, more successful results were identified from analysis of animals in which received melatonin in isolation, regarding biochemical parameters of glutamic oxalacetic transaminase. The prepared slide samples of liver and kidneys from groups submitted to the isolated use of SR and melatonin or the association of these drugs presented no differences, when compared to the control group. DISCUSSION: The administration of the drugs presented chondroprotective effect and prevented from the aggravation of articulate damages, and was not capable of modifying the histology of liver or kidneys. This finding suggests a safe association for the treatment of OA, however it requires further investigation in order to expand therapeutic perspectives regarding improvements of the quality of life of individuals in our society.