Harvesting the Power of Green Synthesis: Gold Nanoparticles Tailored for Prostate Cancer Therapy.

Biosynthetic gold nanoparticles (bAuNPs) present a promising avenue for enhancing bio-compatibility and offering an economically and environmentally responsible alternative to traditional production methods, achieved through a reduction in the use of hazardous chemicals. While the potential of bAuNPs as anticancer agents has been explored, there is a limited body of research focusing on the crucial physicochemical conditions influencing bAuNP production. In this study, we aim to identify the optimal growth phase of Pseudomonas aeruginosa cultures that maximizes the redox potential and coordinates the formation of bAuNPs with increased efficiency. The investigation employs 2,6-dichlorophenolindophenol (DCIP) as a redox indicator. Simultaneously, we explore the impact of temperature, pH, and incubation duration on the biosynthesis of bAuNPs, with a specific emphasis on their potential application as antitumor agents. Characterization of the resulting bAuNPs is conducted using ATR-FT-IR, TEM, and UV-Vis spectroscopy. To gain insights into the anticancer potential of bAuNPs, an experimental model is employed, utilizing both non-neoplastic (HPEpiC) and neoplastic (PC3) epithelial cell lines. Notably, P. aeruginosa cultures at 9 h/OD600 = 1, combined with biosynthesis at pH 9.0 for 24 h at 58 °C, produce bAuNPs that exhibit smaller, more spherical, and less aggregated characteristics. Crucially, these nanoparticles demonstrate negligible effects on HPEpiC cells while significantly impacting PC3 cells, resulting in reduced viability, migration, and lower IL-6 levels. This research lays the groundwork for the development of more specialized, economical, and ecologically friendly treatment modalities.

Antiepileptic effects of long-term intracerebroventricular infusion of angiotensin-(1-7) in an animal model of temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most frequent type of epilepsy and is often refractory to pharmacological treatment. In this scenario, extensive research has identified components of the renin-angiotensin system (RAS) as potential therapeutic targets. Therefore, the aim of the present study was to evaluate the effects of long-term treatment with angiotensin-(1-7) [Ang-(1-7)] in male Wistar rats with TLE induced by pilocarpine (PILO). Rats with TLE were submitted to intracerebroventricular (icv) infusion of Ang-(1-7) (200 ng/kg/h) for 28 days, starting at the first spontaneous motor seizure (SMS). Body weight, food intake, and SMS were evaluated daily. Behavioral tests and hippocampal protein levels were also evaluated at the end of the treatment. Ang-(1-7) treatment reduced the frequency of SMS and attenuated low anxiety levels, increased locomotion/exploration, and reduced body weight gain that was induced by TLE. Moreover, Ang-(1-7) positively regulated the hippocampal levels of antioxidant protein catalase and antiapoptotic protein B-cell lymphoma 2 (Bcl-2), as well as mammalian target of rapamycin (mTOR) phosphorylation, which were reduced by TLE. The hippocampal up-regulation of angiotensin type 1 receptor induced by TLE was also attenuated by Ang-(1-7), while the Mas receptor (MasR) was down-regulated compared with epilepsy. These data show that Ang-(1-7) presents an antiepileptic effect, increasing neuroprotection markers and reducing SMS frequency, body weight, and behavior impairments found in TLE. Therefore, Ang-(1-7) is a promising coadjutant therapeutic option for the treatment of TLE.

Cardiopulmonary Bypass in the Setting of Waldenström's Macroglobulinemia.

Waldenström's Macroglobulinemia (WM) is a rare lymphoma caused by the overproduction of immunoglobulin M (IgM). The elevated level of IgM causes serum hyperviscosity, cold agglutinins, and cryoglobulinemia. Anemia is also present because of impaired production of erythrocytes. For these reasons, placing a patient with WM on cardiopulmonary bypass (CPB) requires careful preparation. In this case, the patient was a 73-year-old male with known Waldenström's disease who required coronary artery bypass graft surgery. This report details the perioperative considerations used for successful CPB on a Waldenström's patient. Critical to this case was the use of plasmapheresis before surgery. Temperature management and acid/base status were carefully controlled. A successful coronary revascularization surgery was performed. Many of the Wadenstrom's disease complications expected on CPB failed to materialize.

Adsorption of the herbicides diquat and difenzoquat on polyurethane foam: Kinetic, equilibrium and computational studies.

This work reports a study about the adsorption of the herbicides diquat and difenzoquat from aqueous medium employing polyurethane foam (PUF) as the adsorbent and sodium dodecylsulfate (SDS) as the counter ion. The adsorption efficiency was shown to be dependent on the concentration of SDS in solution, since the formation of an ion-associate between cationic herbicides (diquat and difenzoquat) and anionic dodecylsulfate is a fundamental step of the process. A computational study was carried out to identify the possible structure of the ion-associates that are formed in solution. They are probably formed by three units of dodecylsulfate bound to one unit of diquat, and two units of dodecylsulfate bound to one unit of difenzoquat. The results obtained also showed that 95% of both herbicides present in 45mL of a solution containing 5.5mgL-1 could be retained by 300mg of PUF. The experimental data were well adjusted to the Freundlich isotherm (r2 ≥ 0.95) and to the pseudo-second-order kinetic equation. Also, the application of Morris-Weber and Reichenberg equations indicated that an intraparticle diffusion process is active in the control of adsorption kinetics.

Polyurethane foam loaded with sodium dodecylsulfate for the extraction of 'quat' pesticides from aqueous medium: Optimization of loading conditions.

The cationic herbicides paraquat, diquat and difenzoquat are largely used in different cultures worldwide. With this, there is an intrinsic risk of environmental contamination when these herbicides achieve natural waters. The goal of this work was to propose a novel and low-cost sorbent for the removal of the cited herbicides from aqueous medium. The proposed sorbent was prepared by loading polyurethane foam with sodium dodecylsulfate. The influence of several parameters (SDS concentration, HCl concentration and shaking time) on the loading process was investigated. The results obtained in this work demonstrated that all studied variables influenced the loading process, having significant effect on the extraction efficiency of the resulted PUF-SDS. At optimized conditions, the PUF was loaded by shaking 200mg of crushed foam with 200mL of a solution containing 5.0×10(-3)molL(-1) SDS and 0.25molL(-1) HCl, for 30min. The obtained PUF-SDS was efficient for removing the three herbicides from aqueous medium, achieving extraction percentages higher than 90%. The sorption process followed a pseudo second-order kinetics, which presented excellent predictive capacity of the amount of herbicide retained with time.

Sorption of the herbicides diquat and difenzoquat from aqueous medium by polymeric resins in the presence of sodium dodecylsulfate: Kinetic and mechanistic study.

The goal of this work was to propose a novel method for the solid-phase extraction of the herbicides diquat (DQT(2+)) and difenzoquat (DFQT(+)) from aqueous medium using polymeric Amberlite XAD-2 and XAD-4 resins in the presence of sodium dodecylsulfate (SDS). The addition of SDS to the medium was of fundamental importance in order to allow the formation of a negatively charged surface able to sorb the cationic solutes. Several factors that could influence the sorption process, such as SDS concentration in the medium, sorbent mass, pH, ionic strength, and initial concentration of the solutes were investigated. Kinetic studies were also performed to model the system and to identify the mechanisms that operate the sorption process of the herbicides. SDS concentration in the medium presented remarkable influence on the extraction efficiency, achieving maximum values when the ratios [SDS]/[herbicide] were approximately 90, for XAD-2, and 22 and 11 for DQT(2+) and DFQT(+), respectively, for XAD-4. The sorption process followed a pseudo second-order kinetic in all cases studied. It was also found that an intraparticle diffusion process controlled exclusively the sorption of the herbicides by the Amberlite XAD-2 and XAD-4 resins in the first 15 min, becoming less active with time.

Modeling, kinetic, and equilibrium characterization of paraquat adsorption onto polyurethane foam using the ion-pairing technique.

We studied the adsorption of paraquat onto polyurethane foam (PUF) when it was in a medium containing sodium dodecylsulfate (SDS). The adsorption efficiency was dependent on the concentration of SDS in solution, because the formation of an ion-associate between the cationic paraquat and the dodecylsulfate anion was found to be a fundamental step in the process. A computational study was carried out to identify the possible structure of the ion-associate in aqueous medium. The obtained data demonstrated that the structure is probably formed from four units of dodecylsulfate bonded to one paraquat moiety. The results showed that 94% of the paraquat present in 45 mL of a solution containing 3.90 × 10(-5) mol L(-1) could be retained by 300 mg of PUF, resulting in the removal of 2.20 mg of paraquat. The experimental data were reasonably adjusted to the Freundlich isotherm and to the pseudo-second-order kinetic model. Also, the application of Morris-Weber and Reichenberg models indicated that both film-diffusion and intraparticle-diffusion processes were active during the control of the adsorption kinetics.

Right and left ventricular function and myocardial scarring in adult patients with sickle cell disease: a comprehensive magnetic resonance assessment of hepatic and myocardial iron overload.

BACKGROUND: Patients with Sickle cell disease (SCD) who receive regular transfusions are at risk for developing cardiac toxicity from iron overload. The aim of this study was to assess right and left cardiac volumes and function, late gadolinium enhancement (LGE) and iron deposits in patients with SCD using CMR, correlating these values with transfusion burden, ferritin and hemoglobin levels. METHODS: Thirty patients with SCD older than 20 years of age were studied in a 1.5 T scanner and compared to age- and sex-matched normal controls. Patients underwent analysis of biventricular volumes and function, LGE and T2* assessment of the liver and heart. RESULTS: When compared to controls, patients with SCD presented higher left ventricular (LV) volumes with decreased ejection fraction (EF) with an increase in stroke volume (SV) and LV hypertrophy. The right ventricle (RV) also presented with a decreased EF and hypertrophy, with an increased end-systolic volume. Although twenty-six patients had increased liver iron concentrations (median liver iron concentration value was 11.83 ± 9.66 mg/g), only one patient demonstrated an abnormal heart T2* < 20 msec. Only four patients (13%) LGE, with only one patient with an ischemic pattern. CONCLUSIONS: Abnormal heart iron levels and myocardial scars are not a common finding in SCD despite increased liver iron overload. The significantly different ventricular function seen in SCD compared to normal suggests the changes in RV and LV function may not be due to the anemia alone. Future studies are necessary to confirm this association.

Bioassay-guided evaluation of Dioscorea villosa - an acute and subchronic toxicity, antinociceptive and anti-inflammatory approach.

BACKGROUND: Dioscorea villosa (DV) has been used in Brazil as an alternative medicine to attenuate menopause symptoms, as well as for the treatment of joint pain and rheumatoid arthritis. In spite of the popular use of DV for the treatment of various disorders, there are limited scientific data regarding safety aspects of this herb. In this regard, we carried out to evaluated both antinociceptive and anti-inflammatory activities in experimental models and assess the toxic effects of the acute (single dose) and subchronic (30 days) oral administration of dry extract of Dioscorea villosa in rodents. METHODS: The LC analyses were performed to assess the presence of the diosgenin in samples of DV. The antinociceptive study of DV was performed using models of acetic acid-induced writhing and formalin-induced pain in mice. The anti-inflammatory study was accomplished by leukocyte migration to the peritoneal cavity. A dry extract of DV was tested at doses of 100, 200 and 400 mg/kg (per os or p.o.). The toxicological properties of the dry extract were evaluated by toxicity assays of acute (5 g/kg, single dose) and subchronic (1 g/kg/day, 30 days) treatment. Haematological, biochemical, and histopathological parameters were studied. The results are expressed as mean ± S.D., and statistical analysis of the data were performed with the Student's t-test or one-way analysis of variance (ANOVA) followed by Tukey's test. In all cases differences were considered significant if p < 0.05. RESULTS: HPLC-DAD analysis of the extract from DV revealed the presence of diosgenin as the major compound. Doses of 200 and 400 mg/kg significantly reduced the amount of acetic acid-induced writhing in relation to the vehicle (p < 0.0001). In the first phase, using the formalin-induced neurogenic pain test, only the 400 mg/kg dose of DV showed significant inhibition of neurogenic pain (p < 0.001). In the second phase, 200 and 400 mg/kg of DV showed significant inhibition of inflammatory pain (p < 0.0001). Significant inhibition of leukocyte migration was observed with doses of 100 (p < 0.001), 200 (p < 0.01) and 400 mg/kg (p < 0.01). Haematological, biochemical and histopathological data obtained in both acute and subchronic toxicological assays revealed only unremarkable changes, which are unlikely to indicate DV toxicity with oral administration. CONCLUSION: We found that DV possesses antinociceptive and anti-inflammatory properties in rodent models. In addition, no acute or subchronic toxicity was evident when the herbal extract was administered orally. These results supporting the folkloric usage of the plant to treat various inflammatory diseases.

Sorption and desorption of sulfentrazone in Brazilian soils.

This study was undertaken to obtain information about the behavior of sulfentrazone in soil by evaluating the sorption and desorption of the herbicide in different Brazilian soils. Batch equilibrium method was used and the samples were analyzed by high performance liquid chromatography. Based on the results obtained from the values of Freundlich constants (Kf), we determined the order of sorption (Haplic Planosol < Red-Yellow Latosol < Red Argisol < Humic Cambisol < Regolitic Neosol) and desorption (Regolitic Neosol < Red Argisol < Humic Cambisol < Haplic Planosol < Red-Yellow Latosol) of sulfentrazone in the soils. The process of pesticide sorption in soils was dependent on the levels of organic matter and clay, while desorption was influenced by the organic matter content and soil pH. Thus, the use of sulfentrazone in soils with low clay content and organic matter (low sorption) increases the probability of contaminating future crops.

Anionic bio-flocculants from sugarcane for purification of sucrose: An application of circular bioeconomy.

In sugar production, polyacrylamide-based anionic flocculants are added for juice treatment, the main objective being to remove impurities that affect the quality of the sugar. However, if they remain in the final product, those polymers can present carcinogenic and neurotoxic actions besides contaminating the soils where the waste is discharged. To overcome this problem, the present study proposes, for the first time, natural flocculants based on cellulose obtained from sugarcane bagasse (residue from sugarcane processing) as substitutes for the flocculants based on polyacrylamide, normally used in sugar cane juice purification. Additionally, cellulose-based flocculants obtained from Acacia wood, developed in a previous study, have also been tested for sugar juice treatment. Acacia wood and sugarcane bagasse were first treated with a choline chloride/levulinic acid solution in a molar ratio of 1:2, at 160 °C, for 4 h. Subsequently, the cellulose-rich samples were modified by a two-stage process (oxidation with sodium periodate followed by reaction with sodium metabisulfite), and polyelectrolytes with different characteristics were produced. The final products obtained were characterized, and their performance in the treatment of sugarcane juice, at different concentrations (10, 50, 100, 250, and 500 mg kg-1), was evaluated and compared to the synthetic commercial flocculant (Flonex, based on polyacrylamide) usually used by the sugarcane industry in Brazil. The substitution of petrol-based flocculants by natural-based ones, obtained from sugarcane residues, is presented for the first time in this study, with very relevant performance of the new flocculants. Overall, it was possible to produce anionic flocculants, modifying the cellulose obtained from different raw materials, which showed good results in the purification of sucrose, when compared with the commercial polyacrylamide normally used. It is also important to stress that, for the first time, a residue from sugarcane industry could be used with success in the purification of the sugar juice itself, which constitutes a major novelty.

Renal function evaluation in patients with American cutaneous leishmaniasis after specific treatment with pentavalent antimonial.

BACKGROUND: Renal evaluation studies are rare in American Cutaneous Leishmaniasis (ACL). The aim of this study is to investigate whether specific treatment reverts ACL-associated renal dysfunction. METHODS: A prospective study was conducted with 37 patients with ACL. Urinary concentrating and acidification ability was assessed before and after treatment with pentavalent antimonial. RESULTS: The patients mean age was 35.6 ± 12 years and 19 were male. Before treatment, urinary concentrating defect (U/Posm <2.8) was identified in 27 patients (77%) and urinary acidification defect in 17 patients (46%). No significant glomerular dysfunction was observed before and after specific ACL treatment. There was no reversion of urinary concentrating defects, being observed in 77% of the patients before and in 88% after treatment (p = 0.344). Urinary acidification defect was corrected in 9 patients after treatment, reducing its prevalence from 40% before to only 16% after treament, (p = 0.012). Microalbuminuria higher than 30 mg/g was found in 35% of patients before treatment and in only 8% after treatment. Regarding fractional excretion of sodium, potassium, calcium, phosphorus and magnesium, there was no significant difference between pre and post-treatment period. CONCLUSION: As previously described, urinary concentrating and acidification defects were found in an important number of patients with ACL. Present results demonstrate that only some patients recover urinary acidification capacity, while no one returned to normal urinary concentration capacity.

Digital transformation: a review on artificial intelligence techniques in drilling and production applications.

The use of digital and artificial intelligence technologies has expanded and influenced business models and the opening of opportunities for the generation of value in several organizations, in a movement known as industry 4.0. The oil industry has been following the path of several other industrial sectors and has implemented digitalization to solve different challenges and problems. The present work, supported by extensive research carried out in the specialized literature, shows relevant applications of digital transformation to solve problems in drilling and production operations during the life cycle of an oil well. The main issues addressed in the research were stuck pipes and hydrate formation. The achievements show that control systems and the various sensors used during drilling and the useful life of an oil well generate data that creates opportunities for the use of computational and artificial intelligence techniques. New technologies associated with digital transformation include smart surveillance systems, real-time monitoring, and intelligent equipment. In a well oil environment, these novelties are associated with fault detection and prediction systems to avoid or reduce problems or accidents that may cause costs or, in extreme cases, lead to the loss of the well. The study also points out that the oil industries, research centers, and universities are increasingly working together to understand the challenges and overcome the problems associated with the implementation and greater use of digital transformation technologies.

Enhancement of the functionality of women with knee osteoarthritis by a gel formulation with Caryocar coriaceum Wittm ("Pequi") nanoencapsulated pulp fixed oil.

Osteoarthritis (OA) is a degenerative joint disease that occurs when there is a change in the mechanical and biological properties of the articular cartilage and the subchondral bone; The condition is more prevalent in women than in men. Pequi oil (PO), which is extracted from the fruits of the pequi tree (Caryocar coriaceum Wittm), is widely used in traditional medicine in the Brazilian northeast for the management of inflammation and joint pain. The aim of this study was to develop a pharmaceutical formulation containing Carbopol® hydrogel nanoencapsulated with pequi pulp fixed oil (PeONC) and evaluate its therapeutic effect on functionality and pain in women with knee osteoarthritis. The study was divided into two stages: Stage 1 - preparation and physico-chemical characterization of the pharmaceutical formulation containing PeONC, cell viability assays and skin irritability testing. Step 2 - A double-blind randomized clinical trial evaluating knee symptoms, quality of life, pressure pain, function, muscle strength and range of motion. The nanoformulation was in a gel form, with a particle size of 209.5 ± 1.06 nm, a pH of 6.23 ± 0.45, a zeta potential of - 23.1 ± 0.4 mV, a polydispersity index of 0.137 ± 0.52, and containing nanocapsules with a spherical shape a polymeric wall and an oily nucleus. The gel showed no cytotoxicity and was not irritating to human skin. The treatment with PeONC increased the strength of the knee flexor and extensor muscles and the total motion range of the knee. In addition, the treatment reduced knee instability, pain, swelling, and locking; There was also an improvement in some items of the SF-36 quality of life questionnaire such as in respect of functional capacity and social aspects. In conclusion, PeONC was found to be a stable, safe formulation with no toxicity in respect of topical use in humans. Additionally, the treatment produced an increase in muscle strength and functionality that was associated with reduced knee symptoms and improved quality of life. Our findings showed that in a group of women treated with PeONC mitigated the symptoms of knee osteoarthritis.

Renal tubular dysfunction in patients with American cutaneous leishmaniasis.

Renal dysfunction seen in patients with American cutaneous leishmaniasis (ACL) has been attributed to the use of antimonials for treatment. To determine whether ACL itself causes tubular dysfunction, we measured renal function in 37 patients with ACL prior to their treatment and compared results to that in 10 healthy volunteers of similar mean age. None of the patients presented with glomerular dysfunction; however, 27 had a urinary concentrating defect. There was no statistical difference between groups in the pre- and post-desmopressin test of urine osmolality, but the post-test urine osmolality of the controls was significantly higher. Urinary AQP2 levels, determined by western blot of isolated exosomes, were found to be significantly lower in patients than in controls, whereas that of the cotransporter (NKCC2) was significantly higher. A urinary acidification defect (post-test pH greater than 5.50 following calcium chloride) was found in 15 patients. Pretest plasma bicarbonate was below normal in 12 patients as was the pretest plasma pH in 14. Expression of the Na/H exchanger (NHE3), H(+)-ATPase, and pendrin were all significantly higher in patients with ACL than in controls. A combined urinary concentration and acidification defect was found in 12 patients. Thus, the urinary concentrating defect of ACL may be caused by decreased AQP2, with increased NKCC2 compensatory. Pendrin upregulation may be related to the urinary acidification defect with increased NHE3 and H(+)-ATPase also compensatory. Hence, ACL can cause asymptomatic renal tubular dysfunction.

MR imaging in deep pelvic endometriosis: a pictorial essay.

Deep pelvic endometriosis is an important gynecologic disorder that is responsible for severe pelvic pain and is defined as subperitoneal invasion that exceeds 5 mm in depth. Deep pelvic endometriosis can affect the retrocervical region, uterosacral ligaments, rectum, rectovaginal septum, vagina, urinary tract, and other extraperitoneal pelvic sites. It is commonly associated with dysmenorrhea, dyspareunia, pelvic pain, urinary tract symptoms, and infertility. Because surgery remains the best therapeutic option for affected patients, the accurate preoperative assessment of the extension of endometriotic disease is extremely important. Pelvic magnetic resonance (MR) imaging is a noninvasive method with high spatial resolution that allows multiplanar evaluation of deep pelvic endometriosis and good tissue characterization, but without the use of ionizing radiation or iodinated contrast agents. MR imaging yields important findings that help grade the disease and identify subperitoneal lesion extension and other associated disease entities, thereby facilitating accurate diagnosis and adequate treatment. Radiologists should be familiar with the MR imaging findings of deep infiltrating endometriosis in various anatomic locations so that they can provide information that allows adequate presurgical counseling.

Anemia and nutritional aspects in adolescent athletes: a cross-sectional study in a reference sport organization.

OBJECTIVE: To assess the association between anemia and nutritional aspects in adolescent athletes from a large sport club. METHODS: This is a cross-sectional study, involving 298 athletes aged between 10 and 17 years, submitted to measurement of skin folds, weight and height, and collection of capillary blood in duplicate to determine hemoglobin values. It was carried out in a random sample composed of athletes from eight sport modalities. RESULTS: Regarding nutritional status, 10.1% of athletes were overweight based on body mass index and 70 (23.5%) athletes had a percentage of body fat classified as high or very high. The prevalence of anemia was 16.4%, being more prevalent in judo (37.1%), basketball (34%) and futsal (20.5%) athletes. Low hemoglobin levels were significantly associated with shorter stature (p=0.006). CONCLUSIONS: There was a significant association between anemia and short stature, suggesting that the athlete's height-weight development may be affected in suboptimal conditions of oxygen distribution.

High-Risk Committee for Cardiac Surgery Decision-Making: Results From 110 Consecutive Patients.

BACKGROUND: This study evaluated our institutional experience in forming a surgeon-based committee to discuss and provide consensus opinion on high-risk cardiac surgical cases. METHODS: The committee consisted of 4 surgeons with at least 1 senior surgeon at any given time with a rotating schedule. Patients with a Society of Thoracic Surgeons predicted risk of mortality above specified thresholds were mandated for referral to the committee in addition to patients referred at the discretion of the surgeon. Kaplan-Meier analysis was used to model survival. RESULTS: A total of 110 consecutive patients were reviewed by the committee. The most common procedure types for referral were isolated coronary artery bypass grafting (47.3%; n = 52) and coronary artery bypass grafting with concomitant aortic valve replacement (19.1%; n = 21). The overall median Society of Thoracic Surgeons predicted risk of mortality for referred patients was 5.35% (interquartile range, 4.07%-7.89%). After group discussion, a total of 62 patients were recommended to proceed with surgery (56.4%). Reasons for declining surgery included consensus that an intervention was not indicated (39.6%; n = 19), that an alternative, nonsurgical procedure was recommended (29.2%; n = 14), that there was continued medical management and reevaluation (18.8%; n = 9), and that the patient was deemed at too high a risk for surgery (12.5%; n = 6). Operative mortality in patients proceeding with surgery was 4.6% (n = 2), with an observed-to-expected mortality of 0.86. The 6-month survival after surgery was 92.2%. CONCLUSIONS: Implementation of a surgeon-based committee to discuss high-risk cases provided a unified voice to referring physicians and facilitated consensus decision-making with acceptable clinical outcomes in a challenging patient cohort.

Nerolidol-beta-cyclodextrin inclusion complex enhances anti-inflammatory activity in arthritis model and improves gastric protection.

Rheumatoid arthritis is an autoimmune inflammatory disease with progressive degradation of cartilage and joints. Additionally, gastric ulcer affects many patients who make prolonged use of non-steroidal anti-inflammatory drugs widely used in the symptomatic treatment of rheumatoid arthritis. Nerolidol, a natural sesquiterpene, has several biological activities including anti-inflammatory and antiulcerogenic action. This study aims to develop and characterize a nerolidol ß-cyclodextrin inclusion complex and to evaluate its activity in an experimental arthritis model. Inclusion complex was prepared by the lyophilization method and characterized by NMR, term analysis, XRD and SEM. Neutrophil migration assays and histopathological analysis were performed on zymosan-induced arthritis model using Swiss mice. And the gastroprotective effect was evaluated in two models of gastric ulcers: induced by ethanol and indomethacin. Inclusion complex showed no cytotoxicity and free nerolidol at a dose of 100 mg/kg (p.o.) in the arthritis model reduced neutrophil migration in 56% in relation to vehicle, and this inhibition was more expressive in the inclusion complex (67%) at the same dose. Histopathological analysis of the joint tissue confirmed the reduction of inflammatory signs. In the ethanol-induced gastric ulcer model, free nerolidol reduced the relative ulcer area more expressively (4.64%) than the inclusion complex (21.3%). However, in the indomethacin induction model, the inclusion complex showed better results in gastric protection compared to free nerolidol. The action of nerolidol complexed in beta-cyclodextrin in reducing arthritis inflammation combined with its gastroprotective action make it a potential new drug.

Dependency structure matrix, genetic algorithms, and effective recombination.

Abstract In many different fields, researchers are often confronted by problems arising from complex systems. Simple heuristics or even enumeration works quite well on small and easy problems; however, to efficiently solve large and difficult problems, proper decomposition is the key. In this paper, investigating and analyzing interactions between components of complex systems shed some light on problem decomposition. By recognizing three bare-bones interactions-modularity, hierarchy, and overlap, facet-wise models are developed to dissect and inspect problem decomposition in the context of genetic algorithms. The proposed genetic algorithm design utilizes a matrix representation of an interaction graph to analyze and explicitly decompose the problem. The results from this paper should benefit research both technically and scientifically. Technically, this paper develops an automated dependency structure matrix clustering technique and utilizes it to design a model-building genetic algorithm that learns and delivers the problem structure. Scientifically, the explicit interaction model describes the problem structure very well and helps researchers gain important insights through the explicitness of the procedure.