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.

Keep Calm: Does parental preoperative anxiety affect post-tonsillectomy pain scores in children?

PURPOSE: To understand if high parental anxiety leads to increased post-tonsillectomy pain in children. METHODS: Prospective study including parents of children aged 3-10 years old submitted to tonsillectomy with or without adenoidectomy. To evaluate anxiety, parents were asked to fill the State-Trait Anxiety Inventory form-Y, with postoperative pain being evaluated with the Wong-Baker FACES pain scale at postoperative days 1, 3 and 7. Parents were also asked to register the number of days during which children took analgesic and the number of analgesic intakes needed. RESULTS: 41 parents were enrolled, of which 95.1% (n = 39) were female with a mean age of 35.64 years (SD 5.751), with 41 children also being enrolled, of which 85.4% of children (n = 35) underwent tonsillectomy and adenoidectomy. 43.9% (n = 18) of parents presented State anxiety scores above the cut-off level and 53.7% (n = 22) above the Trait anxiety scores above the cut-off. Children of parents with high State anxiety presented statistically higher pain scores in both the third (p = 0.035) and the seventh postoperative days (p = 0.006), with significantly longer use of analgesic medication (p = 0.043) being found, as well as a statistically higher number of analgesic intakes (p = 0.045) (Table 4). CONCLUSION: The present study establishes an association between preoperative parental anxiety, postoperative pain scores and the need for longer analgesic use in children undergoing tonsillectomy. This reinforces the importance of reducing parental anxiety and opens the door for further strategies to better post-tonsillectomy outcomes.

Understanding consumer food choices & promotion of healthy and sustainable Mediterranean diet and lifestyle in children and adolescents through behavioural change actions: the DELICIOUS project.

Over the last decades, the abandonment of traditional dietary patterns, such as the Mediterranean diet, represents an important threat for human health and environmental safeguard. The DELICIOUS project aims to promote healthy lifestyles among children and adolescents by implementing activities and tools to increase the adherence to the Mediterranean Diet with an attention to the environmental impacts of the diet. This study protocol describes the DELICIOUS project as a single-arm, uncontrolled behavioural intervention providing formal and non-formal education activities, development of new snacks and recipe reformulation, web/mobile app development, and physical activities to school children and adolescents in five European countries. The project aims to increase awareness of the nutritional benefits and the sustainability aspects of the Mediterranean Diet and to promote consumers' empowerment through an online platform for sustainable and healthy meal planning in the school canteen.

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.

Role of mastoid pneumatization in predicting tympanoplasty results: Will it have the same importance in different age groups?

INTRODUCTION: There are several factors that seem to affect the surgical success rate of tympanoplasty, one of them being the pneumatization of the contralateral mastoid. In the current literature, several studies have been published with classification proposals for temporal bone pneumatization pattern. This study aims to evaluate the role of mastoid air cell extension in relation to the sigmoid sinus in predicting the surgical success of tympanoplasty. MATERIAL AND METHODS: This case-control study was performed on patients diagnosed with chronic otitis media (COM) who underwent type I tympanoplasty. The study group did not close the tympanic membrane, or there was a retraction or lateralization of the graft. The control group consisted of patients with surgical success. RESULTS: No statistically significant difference was found between groups regrading age, gender, perforation side/type, previous nasal surgery, and the presence of chronic otitis media in contralateral ear. A statistically significant difference was found when groups were compared in relation to the degree of pneumatization of the contralateral ear (p = 0.046), and this relationship does not seem to be influenced by age. CONCLUSION: To predict surgical success in terms of tympanic membrane closure in tympanoplasty, classification of contralateral ear pneumatization degree using the sigmoid sinus as a reference seems to be a valid and easy to apply method, and makes it possible to restrict the evaluation of pneumatization to the mastoid, a cell complex that does not seem to change with age.

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.

Septorhinoplasty and the Late Impact on Olfactory Function: A Review and Meta-analysis.

Septorhinoplasty (SRP) is one of the most commonly performed procedures worldwide. There is a recognized debate about the impact of nasal surgery on olfactory function (OF). The study's objective was to assess the effect of SRP on late postoperative OF. A comprehensive review and meta-analysis were employed to assess OF after SRP. All the integrated studies used objective instruments to quantify OF before and after surgery. A literature search was conducted, and the selected works were evaluated, computed, and finally included in a meta-analysis. The risk of bias was assessed using the NIH Guidance for Evaluating the Quality of Before-After (Pre-Post) Studies with No Control Group. Only the latest follow-up OF measurements provided by each research were considered in the analysis. The 95% confidence interval of the effect magnitude for each study was calculated to elucidate effect sizes. Eleven studies were included in the analysis. Five studies reported late OF improvement (45.5%), five reported no alteration in OF (45.5%), and only one study reported OF impairment after SRP (9%). Some works described a transitory decline in OF shortly following surgery, followed by postoperative improvement. A pooled meta-analysis showed that OF was not significantly altered after SRP (p = 0.10) in the late follow-up. SRP surgery seems to constitute a safe procedure concerning OF in the long term. According to research, OF may deteriorate temporarily after surgery with later improvement, sometimes to higher values than baseline. The anticipated evolution of OF after intervention could be discussed during the preoperative consultation for SRP.

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.

Metabolomic Profile and Its Correlation with the Plasmatic Levels of Losartan, EXP3174 and Blood Pressure Control in Hypertensive and Chronic Kidney Disease Patients.

Systemic arterial hypertension (SAH) is one of the most prevalent chronic diseases worldwide and, when dysregulated, may cause serious complications. Losartan (LOS) blocks relevant physiological aspects of hypertension, acting mainly on the reduction of peripheral vascular resistance. Complications of hypertension include nephropathy, in which diagnosis is based on the observation of functional or structural renal dysfunction. Therefore, blood pressure control is essential to attenuate the progression of chronic kidney disease (CKD). In this study, 1H NMR metabolomics were used to differentiate hypertensive and chronic renal patients. Plasmatic levels of LOS and EXP3174, obtained by liquid chromatography coupled with mass-mass spectroscopy, were correlated with blood pressure control, biochemical markers and the metabolomic fingerprint of the groups. Some biomarkers have been correlated with key aspects of hypertension and CKD progression. For instance, higher levels of trigonelline, urea and fumaric acid were found as characteristic markers of kidney failure. In the hypertensive group, the urea levels found could indicate the onset of kidney damage when associated with uncontrolled blood pressure. In this sense, the results point to a new approach to identify CKD in early stages and may contribute to improving pharmacotherapy and reducing morbidity and mortality associated with hypertension and CKD.

Arginine Gemini-Based Surfactants for Antimicrobial and Antibiofilm Applications: Molecular Interactions, Skin-Related Anti-Enzymatic Activity and Cytotoxicity.

The antimicrobial and antibiofilm properties of arginine-based surfactants have been evaluated. These two biological properties depend on both the alkyl chain length and the spacer chain nature. These gemini surfactants exhibit good activity against a wide range of bacteria, including some problematic resistant microorganisms such us methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Moreover, surfactants with a C10 alkyl chain and C3 spacer inhibit the (MRSA) and Pseudomonas aeruginosa biofilm formation at concentrations as low as 8 µg/mL and are able to eradicate established biofilms of these two bacteria at 32 µg/mL. The inhibitory activities of the surfactants over key enzymes enrolled in the skin repairing processes (collagenase, elastase and hyaluronidase) were evaluated. They exhibited moderate anti-collagenase activity while the activity of hyaluronidase was boosted by the presence of these surfactants. These biological properties render these gemini arginine-based surfactants as perfect promising candidates for pharmaceutical and biological properties.

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.

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.

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.

Calcium intake in high-risk pregnant women assisted in a high-complexity hospital.

Pregnancy is characterized by physiological changes. One of these changes involves calcium. During this period, an increased in calcium excretion occurs as well as an increased intestinal absorption and renal reabsorption, so that the adequate growth and development of the fetus can happen. Low calcium intake is associated with chronic diseases, such as diabetes and hypertension, which have negative impact on both mother and fetus. This study aimed to evaluate the average calcium intake of high-risk pregnant women, assisted in a clinic of high complexity service and correlated with chronic diseases. To perform this study, it was used a food frequency questionnaire. As a result, high-risk pregnant women showed daily calcium intake lower than the recommended by DRI during this period. Hypertensive or diabetic pregnant women showed lower average intake of calcium. Significant association between calcium intake and nutritional status was not observed. Calcium supplementation was present, however, at low percentage in the groups with hypertensive pregnant women. To analyze the relation between calcium intake and the comorbidities, as well as calcium intake and the nutritional status of the pregnant women, it was used one-way analysis of variance and Bonferroni multiple comparison. Further studies are required for evaluating other parameters that justify the low calcium intake among this population group, and the definition of pathways for the management of the nutritional deficit considering the possible damage to maternal and neonatal health in the short and long term.

Teduglutide effects on gene regulation of fibrogenesis on an animal model of intestinal anastomosis.

BACKGROUND: Teduglutide is an enterotrophic analog of glucagon-like peptide 2 approved for the rehabilitation of short-bowel syndrome. This study aims to analyze the effects of teduglutide administration on the gene regulation of fibrogenesis during the intestinal anastomotic healing on an animal model. METHODS: Wistar rats (n = 62) were assigned into four groups: "Ileal Resection and Anastomosis" or "Laparotomy," each one subdivided into "Postoperative Teduglutide Administration" or "No Treatment," and sacrificed at the third or at the seventh days, with ileal sample harvesting. Gene expression of matrix components and remodeling factors (matrix metalloproteinases [Mmp] and tissue inhibitors of metalloproteinases [Timp]) and growth factors was studied by real-time polymerase chain reaction. Net collagen deposition was assessed through the Collagen-to-Mmp-to-Timp ratio of fold change of relative gene expression. RESULTS: Gene expression profiles revealed a balance toward net degradation of collagen at the third day of the intestinal anastomotic healing. Teduglutide appeared to be associated with an overall accumulation of collagen at the third day of the anastomotic repair, attributable to the upregulation of Collagen type 1 alpha 1, Collagen type 3 alpha 1, and Collagen type 4 alpha 1, Timp1, and Timp2 and downregulation of Mmp13 and to a net degradation of collagen at the seventh day, derived from repression of Collagen type 3 alpha 1, Collagen type 5 alpha 1 and Timp1 expression. CONCLUSIONS: Teduglutide appeared to be associated with a favorable influence on fibrogenesis at the third day of the intestinal anastomotic repair and to a trend to fibrolysis at the seventh day.

ECHOCARDIOGRAPHIC FINDINGS OF BIDIMENSIONAL MODE, M-MODE, AND DOPPLER OF CLINICALLY NORMAL BLACK-RUMPED AGOUTI (DASYPROCTA PRYMNOLOPHA, WAGLER 1831).

The black-rumped agouti ( Dasyprocta prymnolopha , Wagler 1831) is currently under intense ecologic pressure, which has resulted in its disappearance from some regions of Brazil. Echocardiography is widely used in veterinary medicine but it is not yet part of the clinical routine for wild animals. The objective of the present study was to assess the applicability of the echocardiographic exam in nonanesthetized agouti and to establish normal reference values for echocardiographic measurements in bidimensional mode (2D), M-mode, and Doppler for this species, and a lead II electrocardiogram was simultaneously recorded. Twenty agouti were used in this study. All the echocardiographic measurements were positively correlated with weight (P < 0.05), and there were no significant differences between sexes (P > 0.05). Blood flow velocities in the pulmonary and aortic artery ranged from 67.32-71.28 cm/sec and 79.22-101.84 cm/sec, respectively. The isovolumic relaxation time was assessed in all the animals and ranged from 38.5 to 56.6 ms. The maximum value for the nonfused E and A waves and the Et and At waves was 158 beats/min for both. The results obtained for the morphologic and heart hemodynamic measurements can guide future studies and help in the clinical management of these animals in captivity.

Bioenergetic adaptations of the human liver in the ALPPS procedure - how liver regeneration correlates with mitochondrial energy status.

BACKGROUND: The Associating Liver Partition and Portal Ligation for Staged Hepatectomy (ALPPS) depends on a significant inter-stages kinetic growth rate (KGR). Liver regeneration is highly energy-dependent. The metabolic adaptations in ALPPS are unknown. AIMS: i) Assess bioenergetics in both stages of ALPPS (T1 and T2) and compare them with control patients undergoing minor (miHp) and major hepatectomy (MaHp), respectively; ii) Correlate findings in ALPPS with volumetric data; iii) Investigate expression of genes involved in liver regeneration and energy metabolism. METHODS: Five patients undergoing ALPPS, five controls undergoing miHp and five undergoing MaHp. Assessment of remnant liver bioenergetics in T1, T2 and controls. Analysis of gene expression and protein content in ALPPS. RESULTS: Mitochondrial function was worsened in T1 versus miHp; and in T2 versus MaHp (p < 0.05); but improved from T1 to T2 (p < 0.05). Liver bioenergetics in T1 strongly correlated with KGR (p < 0.01). An increased expression of genes associated with liver regeneration (STAT3, ALR) and energy metabolism (PGC-1α, COX, Nampt) was found in T2 (p < 0.05). CONCLUSION: Metabolic capacity in ALPPS is worse than in controls, improves between stages and correlates with volumetric growth. Bioenergetic adaptations in ALPPS could serve as surrogate markers of liver reserve and as target for energetic conditioning.

Mitochondrial bioenergetics and posthepatectomy liver dysfunction.

BACKGROUND: Liver regeneration requires an enormous energy supply. Experimental evidence suggests that mitochondrial function is of paramount importance for liver regeneration. However, this has not been investigated in the clinical setting. We aimed to: (i) evaluate changes in mitochondrial function during hepatectomy, especially after hepatic pedicle clamping; and (ii) correlate these changes with postoperative hepatocellular function and clinical outcome. MATERIALS AND METHODS: Prospective study of thirty patients undergoing hepatectomy. Measurement of mitochondrial membrane potential, respiration and adenosine triphosphate content in intra-operative liver biopsies performed in nonresected parenchyma. Correlation of findings with duration of hepatic pedicle clamping, postoperative markers of hepatocellular necrosis and function (aminotransferases, arterial lactate, international normalized ratio, bilirubin), and morbidity. RESULTS: Longer hepatic pedicle clamping was associated with worse mitochondrial depolarization (r = -0·519; P = 0·011) and longer lag phase (r = 0·568; P = 0·006). Higher postoperative peak aminotransferases, international normalized ratio and bilirubin correlated with worse mitochondrial function (P < 0·05). After major hepatectomy, mitochondrial respiration correlated with postoperative arterial lactate clearance (r = 0·756; P = 0·049). Mitochondrial bioenergetic parameters were significantly decreased in patients with liver-specific morbidity and postoperative liver failure (P < 0·05). On multivariate analysis, decrease in mitochondrial potential was an independent risk factor for liver-specific morbidity (OR = 13·7; P = 0·043). Worse lag phase was highly predictive of posthepatectomy liver failure (area under the curve: 0·933; P = 0·008). CONCLUSIONS: There is a relationship between mitochondrial function, duration of hepatic pedicle clamping and clinical outcome after hepatectomy. Mitochondrial bioenergetics can potentially translate into clinical practice, assisting in earlier diagnosis of postoperative liver dysfunction, and as a target for future pharmacological therapies.

Oncostatin M and leukaemia inhibitory factor trigger signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2 pathways but result in heterogeneous cellular responses in trophoblast cells.

Leukaemia inhibitory factor (LIF) and oncostatin M (OSM) are pleiotropic cytokines present at the implantation site that are important for the normal development of human pregnancy. These cytokines share the cell membrane receptor subunit gp130, resulting in similar functions. The aim of this study was to compare the response to LIF and OSM in several trophoblast models with particular regard to intracellular mechanisms and invasion. Four trophoblast cell lines with different characteristics were used: HTR-8/SVneo, JEG-3, ACH-3P and AC1-M59 cells. Cells were incubated with LIF, OSM (both at 10ngmL(-1)) and the signal transducer and activator of transcription (STAT) 3 inhibitor S3I-201 (200µM). Expression and phosphorylation of STAT3 (tyr(705)) and extracellular regulated kinase (ERK) 1/2 (thr(202/204)) and the STAT3 DNA-binding capacity were analysed by Western blotting and DNA-binding assays, respectively. Cell viability and invasiveness were assessed by the methylthiazole tetrazolium salt (MTS) and Matrigel assays. Enzymatic activity of matrix metalloproteinase (MMP)-2 and MMP-9 was investigated by zymography. OSM and LIF triggered phosphorylation of STAT3 and ERK1/2, followed by a significant increase in STAT3 DNA-binding activity in all tested cell lines. Stimulation with LIF but not OSM significantly enhanced invasion of ACH-3P and JEG-3 cells, but not HTR-8/SVneo or AC1-M59 cells. Similarly, STAT3 inhibition significantly decreased the invasiveness of only ACH-3P and JEG-3 cells concomitant with decreases in secreted MMP-2 and MMP-9. OSM shares with LIF the capacity to activate ERK1/2 and STAT3 pathways in all cell lines tested, but their resulting effects are dependent on cell type. This suggests that LIF and OSM may partially substitute for each other in case of deficiencies or therapeutic interventions.

Parameter space of experimental chaotic circuits with high-precision control parameters.

We report high-resolution measurements that experimentally confirm a spiral cascade structure and a scaling relationship of shrimps in the Chua's circuit. Circuits constructed using this component allow for a comprehensive characterization of the circuit behaviors through high resolution parameter spaces. To illustrate the power of our technological development for the creation and the study of chaotic circuits, we constructed a Chua circuit and study its high resolution parameter space. The reliability and stability of the designed component allowed us to obtain data for long periods of time (∼21 weeks), a data set from which an accurate estimation of Lyapunov exponents for the circuit characterization was possible. Moreover, this data, rigorously characterized by the Lyapunov exponents, allows us to reassure experimentally that the shrimps, stable islands embedded in a domain of chaos in the parameter spaces, can be observed in the laboratory. Finally, we confirm that their sizes decay exponentially with the period of the attractor, a result expected to be found in maps of the quadratic family.