Maslinic acid solid lipid nanoparticles as hydrophobic anticancer drug carriers: Formulation, in vitro activity and in vivo biodistribution.

Maslinic acid (MA) is a natural pentacyclic triterpenoid with inherent antitumor activity which has a very low solubility in water. MA solid lipid nanoparticles (SLNs) were prepared using Poloxamer 407 and Dicarboxylic acid-Poloxamer 407 as surfactants. Both MA SLNs are monodisperse, with sizes around 130 nm, and stable. Curcumin has been encapsulated in both types of nanoparticles without altering their colloidal properties. Moreover, SLNs greatly improve the solubility of MA and Curcumin. The cytotoxicity of MA and SLNs has been evaluated in BxPC3 human pancreatic cancer cells, MCF7 human breast cancer cells, and in a human fibroblast primary cell line. MA shows higher cytotoxic effect in BxPC3 and MCF7 cancer cells than in human primary fibroblasts. Nile Red loaded MA SLNs are quickly uptaken by BxPC3 and MCF7 cells, and show different cytoplasmic distributions depending on the cellular line. The oral or intravenous administration of MA SLNs in mice does not report any toxic effect, and the intravenous administration of fluorescent MA SLNs shows a homogeneous distribution in mice, without site-specific accumulation. Results suggest the great potential of MA SLNs as nanocarriers of anticancer drugs and as promising targeted theranostic nanodevices.

Mixing Controlled Adsorption at the Liquid-Solid Interfaces in Unsaturated Porous Media.

The unsaturated zone, located between the soil surface and the phreatic level, plays an important role in defining the fate of any substance entering the subsoil. In addition to the processes of flow and transport taking place in the liquid phase, surface reactions such as adsorption to the solid phase may occur and increase the residence time of the substance entering the system. In this study, we aim to understand the pore-scale mechanisms that control adsorption in unsaturated systems. We combine 2D pore-scale experimental images with numerical simulations to analyze flow, transport, and adsorption under different liquid saturation degrees. We demonstrate the role of mixing on adsorption at the liquid-solid interfaces by analyzing the deformation in time of a pulse-injected surfactant. We also analyze the impact of the isotherm functional shape and the inclusion of the liquid-gas interfaces as adsorption sites on this surface reaction. The enhancement of mixing as saturation decreases is accompanied by a reduction in the amount of adsorbed mass, located mainly along preferential flow paths, where the solute is primarily transported. For the same isotherm, a nonlinear behavior of adsorption as a function of liquid saturation has been observed. This is explained by the nonlinear variation of the volume fraction of liquid behaving as preferential path or stagnation zone as liquid saturation decreases, despite the linear decrease in the surface area of solids accessible for adsorption. Supplementary Information: The online version contains supplementary material available at 10.1007/s11242-022-01747-x.

Synthesis, Optical Properties, and Antiproliferative Evaluation of NBD-Triterpene Fluorescent Probes.

A fluorescent labeling protocol for hydroxylated natural compounds with promising antitumor properties has been used to synthesize, in yields of 72-86%, 12 derivatives having fluorescent properties and biological activity. The reagent used for the synthesis of these fluorescent derivatives was 7-nitrobenzo-2-oxa-1,3-diazole chloride (NBD-Cl). The linkers employed to bind the NBD-Cl reagent to the natural compounds were ω-amino acids (Aa) of different chain lengths. The natural triterpene compounds chosen were oleanolic and maslinic acid, as their corresponding 28-benzylated derivatives. Thus, 12 NBD-Aa-triterpene conjugates have been studied for their optical fluorescence properties and their biological activities against cell proliferation in three cancer cell lines (B16-F10, HT-29, and HepG2), compared with three nontumor cell lines (HPF, IEC-18, and WRL68) from different tissues. The results of the fluorescence study have shown that the best fluorescent labels are those in which the ω-amino acid chain is shorter, and the carboxylic group is not benzylated. Analysis by confocal microscopy showed that these compounds were rapidly incorporated into cells in all three cancer cell lines, with these same derivatives showing the highest toxicity against the cancer cell lines tested. Then, the fluorescent labeling of these NBD-Aa-triterpene conjugates enabled their uptake and subcellular distribution to be followed in order to probe in detail their biological properties at the cellular and molecular level.

Laparoscopic appendectomy in complicated appendicitis with compromised appendix base: a retrospective cohort study.

BACKGROUND: Patients with compromised appendix base constitute a subgroup of patients with complicated appendicitis, and there is few available information. OBJECTIVE: To study the frequency of stump leaks and fistulae in patients with complicated appendicitis with compromised stump. METHOD: This is an observational, retrospective study of patients that underwent laparoscopic appendectomy with compromised appendix stump. RESULTS: From 2015 to 2019, 158 patients with complicated appendicitis were operated, of them 54 had compromised base or stump. There were 66.7% men, with a mean age of 38.7 years. For stump closure, a simple knot was employed in 57.4%, and in 42.6% an invaginated suture was employed. Regarding complications, 16.7% developed intraabdominal abscess, 7.4% ileus and 7.4% had wound infection. We found one stump leak and one stump fistula. The mean length of stay was 5.4 days (range: 1-20). There were 5 reoperations, 4 for abscess drainage and 1 for stump leak. CONCLUSIONS: Patients with acute complicated appendicitis with compromised appendicular base, laparoscopic surgery either with simple knot or with invaginated suture resulted in low frequency of stump leaks and fistula.

ANTECEDENTES: Los pacientes con base apendicular comprometida constituyen un subgrupo de pacientes con apendicitis complicada y existe poca información al respecto. OBJETIVO: Conocer la frecuencia de fístulas y fugas fecales en pacientes con apendicitis complicada con base apendicular comprometida. MÉTODO: Se trata de un estudio observacional, retrospectivo y transversal de pacientes operados de apendicectomía laparoscópica con base apendicular comprometida. RESULTADOS: De 2015 a 2019 se encontraron 158 casos de apendicitis complicada, de los cuales 54 tenían la base apendicular comprometida. Hubo predominio de varones (66.7%) y la edad media fue de 38.7 años. En el 57.4% de los casos se realizó un nudo simple y en el 42.6% un punto transfictivo con invaginación del muñón. En relación con las complicaciones, el 16.7% desarrollaron abscesos intraabdominales, el 7.4% íleo y el 7.4% infección de herida. Hubo un paciente con fuga del muñón y un paciente con fístula cecal. El tiempo medio de estancia hospitalaria fue de 5.4 días (rango: 1-20). Se realizaron cinco reintervenciones: cuatro para drenaje de absceso intraabdominal y una por fuga del muñón. CONCLUSIONES: En los pacientes con base apendicular comprometida, el manejo laparoscópico con ligadura simple o con punto transfictivo resulta en una baja frecuencia de fuga y fístula del muñón apendicular.

Efficient In Vitro and In Vivo Anti-Inflammatory Activity of a Diamine-PEGylated Oleanolic Acid Derivative.

Recent evidence has shown that inflammation can contribute to all tumorigenic states. We have investigated the anti-inflammatory effects of a diamine-PEGylated derivative of oleanolic acid (OADP), in vitro and in vivo with inflammation models. In addition, we have determined the sub-cytotoxic concentrations for anti-inflammatory assays of OADP in RAW 264.7 cells. The inflammatory process began with incubation with lipopolysaccharide (LPS). Nitric oxide production levels were also determined, exceeding 75% inhibition of NO for a concentration of 1 µg/mL of OADP. Cell-cycle analysis showed a reversal of the arrest in the G0/G1 phase in LPS-stimulated RAW 264.7 cells. Furthermore, through Western blot analysis, we have determined the probable molecular mechanism activated by OADP; the inhibition of the expression of cytokines such as TNF-α, IL-1ß, iNOS, and COX-2; and the blocking of p-IκBα production in LPS-stimulated RAW 264.7 cells. Finally, we have analyzed the anti-inflammatory action of OADP in a mouse acute ear edema, in male BL/6J mice treated with OADP and tetradecanoyl phorbol acetate (TPA). Treatment with OADP induced greater suppression of edema and decreased the ear thickness 14% more than diclofenac. The development of new derivatives such as OADP with powerful anti-inflammatory effects could represent an effective therapeutic strategy against inflammation and tumorigenic processes.

COVID-19 and Canadian Gastroenterology Trainees.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted endoscopy services and education worldwide. This study aimed to characterize the impact of COVID-19 on gastroenterology trainees in Canada. METHODS: An analysis of Canadian respondents from the international EndoTrain survey, open from April 11 to May 2 2020 and distributed by program directors, trainees, and national and international gastroenterology societies' representatives, was completed. The survey included questions on monthly endoscopy volume, personal protective equipment availability, trainee well-being and educational resources. The primary outcome was change in procedural volume during the COVID-19 pandemic. Secondary outcomes included trainee's professional and personal concerns, anxiety and burnout. RESULTS: Thirty-four Canadian trainees completed the survey. Per month, participants completed a median of 30 esophagogastroduodenoscopies (interquartile range 16 to 50) prior to the pandemic compared to 2 (0 to 10) during the pandemic, 20 (8 to 30) compared to 2 (0 to 5) colonoscopies and 3 (1 to 10) compared to 0 (0 to 3) upper gastrointestinal bleeding procedures. There was a significant decrease in procedural volumes between the pre-COVID-19 and COVID-19 time periods for all procedures (P < 0.001). Thirty (88%) trainees were concerned about personal COVID-19 exposure, 32 (94%) were concerned about achieving and/or maintaining clinical competence and 24 (71%) were concerned about prolongation of training time due to the pandemic. Twenty-six (79%) respondents experienced some degree of anxiety, and 10 (31%) experienced some degree of burnout. CONCLUSION: The COVID-19 pandemic has substantially impacted gastroenterology trainees in Canada. As the pandemic eases, it important for gastrointestinal programs to adapt to maximize resident learning, maintain effective clinical care and ensure development of endoscopic competence.

Synthesis and Biological Activity of Triterpene-Coumarin Conjugates.

A set of 12 maslinic acid-coumarin conjugates was synthesized, with 9 being maslinic acid-diamine-coumarin conjugates at the C-28 carboxylic acid group of triterpene acid and the other three being maslinic acid-coumarin conjugates at C-2/C-3 and/or C-28 of the triterpene skeleton. The cytotoxic effects of these 12 triterpene conjugates were evaluated in three cancer cell lines (B16-F10, HT29, and Hep G2) and compared, respectively, with three nontumor cell lines from the same or similar tissue (HPF, IEC-18, and WRL68). The most potent cytotoxic results were achieved by a conjugate with two molecules of coumarin-3-carboxylic acid coupled through the C-2 and C-3 hydroxy groups of maslinic acid. This conjugate showed submicromolar IC50 values in two of the three cancer cell lines tested (0.6, 1.1, and 0.9 µM), being between 110- and 30-fold more effective than its corresponding precursor. Furthermore, this conjugate (10) showed percentages of cell viability for the three nontumor lines of 90%. Four maslinic acid-coumarin conjugates displayed apoptotic effects in the treated cells, with total apoptosis rates of between 40 and 85%, relative to the control. Almost all the compounds assayed caused cell-cycle arrest in all cancer cell lines, increasing the number of these cells in the G0/G1 phase.

Peroral endoscopic myotomy as treatment for Zenker's diverticulum (Z-POEM): a multi-center international study.

BACKGROUND: Peroral endoscopic myotomy for the treatment of Zenker's diverticulum (Z-POEM) is a novel technique that has been described in several recent reports. This method utilizes the third space (submucosal layer) to create a tunnel to facilitate complete visualization of the septum and hence cutting it entirely. Conventional endoscopic septotomy carries the risk of recurrence due to incomplete visualization of the septum. While surgical correction is a risky and lengthy procedure in old comorbid patients with Zenker's diverticulum. The aim of this study is to assess the efficacy and safety of Z-POEM. METHODS: The study enrolled 24 patients diagnosed with Zenker's diverticulum (ZD) who underwent Z-POEM at seven independent endoscopy centers in five different countries. RESULTS: Mean patient age ± standard deviation (SD) was 74.3 ± 11 years. Most of the patients were males (n = 20, 83.3%); four (16.7%) were females. More than 50% of the patients (n = 14, 58.3%) had associated comorbidities. The mean size of the diverticula was 4 cm (range 2-7 cm). The Kothari-Haber Score was used to assess clinical symptoms; values ranged from 6 to 14 (median = 9). We achieved 100% technical success with a median procedure time of 61 min and no adverse events. Median hospital stay was 1 day (range 1-5 days). There is a significant reduction in the Kothari-Haber Score after Z-POEM (P < 0.0001). Technical success was achieved in 100% of the patients. Clinical success was achieved in 23/24 (95.8%) of the patients with a median follow-up of 10 months (range 6-24 months). CONCLUSION: Z-POEM is a safe and effective modality for managing ZD.

A Diamine-PEGylated Oleanolic Acid Derivative Induced Efficient Apoptosis through a Death Receptor and Mitochondrial Apoptotic Pathway in HepG2 Human Hepatoma Cells.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Our recent studies have shown that the diamine-(PEG)ylated oleanolic acid (OADP) has strong anti-tumor effects in HCCs. In this study, we evaluated the anti-tumor mechanisms of OADP in the HepG2 HCC cell line. The cytotoxicity results showed that HepG2 cell viability was markedly reduced, with a very low 50% of cell growth inhibitory concentration (IC50, 0.14 µg/mL). We then investigated the anti-tumor mechanisms of OADP in HepG2 cells. The flow-cytometry analysis was used to evaluate cell apoptosis, indicating that 74-95% of cells were apoptotic. OADP caused cell cycle arrest in the G0/G1 phase and the loss of the mitochondrial membrane potential (MMP). Western blot analysis was performed to assess the expression levels of key proteins associated with the underlying molecular mechanism. The results showed the clear upregulation of caspase-8, caspase-9, caspase-3, Bak, p21, and p53, accompanied by the downregulation of Bcl-2. Similar results were obtained by the cotreatment with OADP and the c-Jun N-terminal kinase (JNK) inhibitor SP600125. Agents such as OADP, which are capable of activating extrinsic and intrinsic apoptotic pathways, may represent potential HCC cancer therapies.

Impact of COVID-19 on endoscopy trainees: an international survey.

BACKGROUND AND AIMS: Although coronavirus disease 2019 (COVID-19) has affected endoscopy services globally, the impact on trainees has not been evaluated. We aimed to assess the impact of COVID-19 on procedural volumes and on the emotional well-being of endoscopy trainees worldwide. METHODS: An international survey was disseminated over a 3-week period in April 2020. The primary outcome was the percentage reduction in monthly procedure volume before and during COVID-19. Secondary outcomes included potential variation of COVID-19 impact between different continents and rates and predictors of anxiety and burnout among trainees. RESULTS: Across 770 trainees from 63 countries, 93.8% reported a reduction in endoscopy case volume. The median percentage reduction in total procedures was 99% (interquartile range, 85%-100%), which varied internationally (P < .001) and was greatest for colonoscopy procedures. Restrictions in case volume and trainee activity were common barriers. A total of 71.9% were concerned that the COVID-19 pandemic could prolonged training. Anxiety was reported in 52.4% of respondents and burnout in 18.8%. Anxiety was independently associated with female gender (odds ratio [OR], 2.15; P < .001), adequacy of personal protective equipment (OR, 1.75; P = .005), lack of institutional support for emotional health (OR, 1.67; P = .008), and concerns regarding prolongation of training (OR, 1.60; P = .013). Modifying existing national guidelines to support adequate endoscopy training during the pandemic was supported by 68.9%. CONCLUSIONS: The COVID-19 pandemic has led to restrictions in endoscopic volumes and endoscopy training, with high rates of anxiety and burnout among endoscopy trainees worldwide. Targeted measures by training programs to address these key issues are warranted to improve trainee well-being and support trainee education.

Mass fluxes of nitrogen and phosphorus through water reclamation facilities: Case study of biological nutrient removal, aerobic sludge digestion, and sidestream recycle.

At water reclamation facilities, recycling of nutrients (nitrogen and phosphorus) from solids-handling processes to the mainstream treatment process can have detrimental effects on biological nutrient removal systems. In this study, mass fluxes of nitrogen and phosphorus were quantified through the treatment trains at the Northwest Regional Water Reclamation Facility (NWRWRF) and the adjoining Biosolids Management Facility (BMF), which receives sludge from several water reclamation facilities in Hillsborough County, Florida. The driving objectives were to determine (a) whether the return stream from BMF to NWRWRF (i.e., the "sidestream") represents a significant source of nitrogen and phosphorus to NWRWRF, and (b) whether the sidestream return from BMF is interfering with biological nutrient removal processes at NWRWRF. We determined that nearly half of the overall phosphorus flux into NWRWRF is recycled from the BMF sidestream. This leads to an increased cost of treatment, for example, for alum used in phosphorus removal at NWRWRF. In contrast to phosphorus, the flux of nitrogen from BMF to NWRWRF is small (~3%) compared with the flux of nitrogen entering NWRWRF in raw wastewater. However, nitrogen in the sidestream is mostly in the form of nitrate, which prevents anaerobic conditions from developing in the fermentation basin at NWRWRF, and thereby interferes with the enhanced biological phosphorus removal (EBPR) process. Some measurements suggest that fermentation and release of phosphorus may occur in the return activated sludge line (despite the relatively short residence time in that line), which supports EBPR and may partially compensate for anoxic (denitrifying) conditions in the fermentation basin. Therefore, overall, NWRWRF is able to meet its permit limits for phosphorus through a combination of EBPR and alum addition. Although the fluxes measured here are particular to the treatment systems under consideration, the general trends observed are likely to apply to many similar facilities that employ biological nutrient removal, aerobic digestion, and sidestream recycle, particularly those with regional biosolids management facilities. We recommend that such facilities consider (a) removal or recovery of phosphorus from their sidestreams and (b) returning sidestreams downstream of fermentation basins to avoid inhibition of EBPR processes. PRACTITIONER POINTS: Sidestreams from aerobic digestion can represent significant sources of phosphorus to mainstream wastewater treatment. Recycle of nitrate in aerobic digestion sidestreams can interfere with enhanced biological phosphorus removal (EBPR) during mainstream treatment. Fermentation of return activated sludge (RAS) can support EBPR, even under short average hydraulic residence times (minutes).

Oleanolic Acid Derivatives as Potential Inhibitors of HIV-1 Protease.

Pentacyclic triterpenes, such as oleanolic acid (I), are promising scaffolds for diversification through the use of combinatorial methods to obtain derivatives that improve their biological properties, increasing their bioavailability and enhancing their therapeutic efficacy. The purpose of this study was to evaluate the influence that derivatives of oleanolic acid, conjugated with one or two amino acids and an acyl group, might exert on HIV-1 protease inhibition. The in vitro studies conducted suggested that the presence of a carboxyacyl group generally improves the inhibition of HIV-1 protease, especially when a phthaloyl group is present, with IC50 concentration values below 5 µM. The gain in activity of three 3-phthaloyl derivatives, with sub-micromolar IC50 values, was between 60- and 100-fold more active than oleanolic acid. A molecular docking study has also been performed to elucidate the mode of binding to the protease by these oleanolic acid derivatives. In general, the derivatives that exhibited the highest inhibitory activity of HIV-1 protease also showed the highest binding energies in docking simulations. The overall results suggest that the coupling of one or two amino acids and a phthaloyl group to oleanolic acid improves HIV-1 protease inhibition, implying that these triterpene derivatives may be promising antiviral agents against HIV.

Novel Oleanolic and Maslinic Acid Derivatives as a Promising Treatment against Bacterial Biofilm in Nosocomial Infections: An in Vitro and in Vivo Study.

Oleanolic acid (OA) and maslinic acid (MA) are pentacyclic triterpenic compounds that abound in industrial olive oil waste. These compounds have renowned antimicrobial properties and lack cytotoxicity in eukaryotic cells as well as resistance mechanisms in bacteria. Despite these advantages, their antimicrobial activity has only been tested in vitro, and derivatives improving this activity have not been reported. In this work, a set of 14 OA and MA C-28 amide derivatives have been synthesized. Two of these derivatives, MA-HDA and OA-HDA, increase the in vitro antimicrobial activity of the parent compounds while reducing their toxicity in most of the Gram-positive bacteria tested, including a methicillin-resistant Staphylococcus aureus-MRSA. MA-HDA also shows an enhanced in vivo efficacy in a Galleria mellonella invertebrate animal model of infection. A preliminary attempt to elucidate their mechanism of action revealed that these compounds are able to penetrate and damage the bacterial cell membrane. More significantly, their capacity to reduce antibiofilm formation in catheters has also been demonstrated in two sets of conditions: a static and a more challenged continuous-flow S. aureus biofilm.

Microstructure Design for Fast Lifetime Measurements of Magnetic Tunneling Junctions.

The estimation of the reliability of magnetic field sensors against failure is a critical point concerning their application for industrial purposes. Due to the physical stochastic nature of the failure events, this can only be done by means of a statistical approach which is extremely time consuming and prevents a continuous observation of the production. Here, we present a novel microstructure design for a parallel measurement of the lifetime characteristics of a sensor population. By making use of two alternative designs and the Weibull statistical distribution function, we are able to measure the lifetime characteristics of a CoFeB/MgO/CoFeB tunneling junction population. The main parameters governing the time evolution of the failure rate are estimated and discussed and the suitability of the microstructure for highly reliable sensor application is proven.

Regional Specialization of Pyramidal Neuron Morphology and Physiology in the Tree Shrew Neocortex.

The mammalian cerebral cortex is divided into different areas according to their function and pattern of connections. Studies comparing primary visual (V1) and prefrontal cortex (PFC) of primates have demonstrated striking pyramidal neuron (PN) specialization not present in comparable areas of the mouse neocortex. To better understand PFC evolution and regional PN specialization, we studied the tree shrew, a species with a close phylogenetic relationship to primates. We defined the tree shrew PFC based on cytoarchitectonic borders, thalamic connectivity and characterized the morphology and electrophysiology of layer II/III PNs in V1 and PFC. Similar to primates, the PFC PNs in the tree shrew fire with a regular spiking pattern and have larger dendritic tree and spines than those in V1. However, V1 PNs showed strikingly large basal dendritic arbors with high spine density, firing at higher rates and in a more varied pattern than PFC PNs. Yet, unlike in the mouse and unreported in the primate, medial prefrontal PN are more easily recruited than either the dorsolateral or V1 neurons. This specialization of PN morphology and physiology is likely to be a significant factor in the evolution of cortex, contributing to differences in the computational capacities of individual cortical areas.

Quantitative NMR analysis of L-Dopa in seeds from two varieties of Mucuna pruriens.

INTRODUCTION: L-Dopa, a key neurotransmitter used to treat neural disorders such as Parkinson's disease, is found in the seeds of the genus Mucuna at a sufficient concentration for possible commercial use. OBJECTIVE: To develop a simple and reliable method to extract L-Dopa from M. pruriens seeds in an aqueous medium and then quantitate this compound using a 1 H qNMR method (internal standard); and also to evaluate the accuracy and reproducibility of this method with an NMR calibration curve. METHODOLOGY: The extraction method of L-Dopa from M. pruriens was optimized. The quantitation with single point quantitative NMR (qNMR) and NMR calibration curve was based on the resonance properties of the main functional groups of the L-Dopa molecule, in particular the signals of the three aromatic protons, which were compared with the signal of an internal standard such as syringic acid. The accuracy (precision and trueness) and reproducibility of both NMR techniques were evaluated. RESULTS: The methods of single point qNMR and NMR calibration curve, applied to the seeds of two M. pruriens varieties, gave very similar L-Dopa contents: 3.0-3.2% and 3.0-3.1%, respectively. CONCLUSION: The statistical analysis confirmed the accuracy and reproducibility of this single point qNMR method (internal standard) for determining L-Dopa, as well as other commercial preparations of this species, without performing an NMR calibration curve.

Semisynthesis of ω-Hydroxyalkylcarbonate Derivatives of Hydroxytyrosol as Antitrypanosome Agents.

Several lipophilic ω-hydroxyalkylcarbonate hydroxytyrosol derivatives and also their corresponding dimeric derivatives have been synthesized, coupling the primary hydroxy group of this phenolic compound with several terminal diols of different chain lengths, by the use of a carbonate linker. The trypanocidal activity and cytotoxicity of these ω-hydroxyalkylcarbonate derivatives of hydroxytyrosol and known alkylcarbonate derivatives of hydroxytyrosol were assessed. Three of the hydroxytyrosol alkylcarbonate derivatives were active against Trypanosoma brucei: two with an alkyl chain of average size (0.2 and 0.5 µM) and another with a double bond in the alkyl chain (0.4 µM). These values suggest an increase in activity with respect to hydroxytyrosol (264-, 90-, and 116-fold, respectively). Furthermore, these compounds showed high selectivity indices against MRC-5, a nontumor human cell line (62, 71, and 39, respectively). Some other ω-hydroxyalkylcarbonate and alkylcarbonate derivatives of hydroxytyrosol were also active against T. brucei within a low micromolar range (about 1 µM).

Diamine and PEGylated-diamine conjugates of triterpenic acids as potential anticancer agents.

A set of 18 amide derivatives of oleanolic or maslinic acid has been semi-synthesised. Twelve were diamine conjugates at C-28 of these triterpenic acids and the other six were PEGylated-diamine derivatives. The cytotoxic effects of these 18 triterpenic derivatives in three cancer-cell lines (B16-F10, HT29, and Hep G2) have been assayed, and have been compared to three non-tumour cell lines of the same or a similar tissue (HPF, IEC-18, and WRL68). The cell viability percentages for the non-tumour HPF line for almost all diamine conjugates of the tested triterpenic acids ranged from 81% to 94%. The best cytotoxic results were achieved with the diamine conjugates of oleanolic or maslinic acid with the shortest and the longest diamine chain (IC50 values from 0.76 µM to 1.76 µM), on the B16-F10 cell line, being between 140- and 20-fold more effective than their corresponding precursors. Four diamine conjugates of these triterpenic acids showed apoptotic effects on treated cells of the B16-F10 line, with total apoptosis rates, relative to control, of between 73% and 90%. The DNA-histogram analysis revealed that all compounds tested produced cell-cycle arrest in B16-F10 cells, increasing the number of these cells in the S phase. All the compounds analysed, except one, did not cause changes in mitochondrial-membrane potential during apoptosis of the B16-F10 cancer cells, suggesting an activation of the extrinsic apoptotic pathway for these compounds.

Assessment of the Prosthetic Replacement of Ocular Surface Ecosystem (PROSE) scleral lens on visual acuity for corneal irregularity and ocular surface disease.

PURPOSE: To describe changes in visual acuity in patients fit with the Prosthetic Replacement of Ocular Surface Ecosystem (PROSE) with irregular corneas compared to those with ocular surface disease, as well as describe patient demographics and fitting indications for PROSE at an academic medical center. METHODS: A retrospective chart review from 2010 to 2016 on a total of 825 eyes from 493 patients fitted with a PROSE lens, and grouped by etiology, either irregular cornea/dystrophy or ocular surface disease and associated sub-etiologies. We compared best corrected visual acuity (BCVA) before and after PROSE fitting. RESULTS: The irregular cornea group (n = 262 eyes) included corneal scar (n = 57), dystrophy (n = 17), post-operative corneal irregularity (n = 70), and primary ectasia (n = 118). The OSD group included 563 eyes. For all etiologies combined, mean BCVA prior to PROSE fitting compared to after improved by 0.28 logMAR (p < .001). In the irregular cornea group, the mean BCVA improved by 0.46 logMAR (p < .001), while the improvement in BCVA for the OSD group was 0.20 logMAR (p < .001). All etiologies in the irregular cornea group demonstrated improvement in BCVA (p < .05) with the exception of post-PRK (n = 2). BCVA improvement was found for all sub-etiologies in the OSD subgroup (p < .05). CONCLUSIONS: PROSE treatment had a positive impact on visual acuity for a wide range of corneal irregularities and ocular surface disease, suggesting that PROSE lenses may offer improvements in visual acuity without risks inherent to surgery.

Robotic-assisted Roux-en-Y hepaticojejunostomy after bile duct injury.

BACKGROUND: The Da Vinci Robotic Surgical System has positioned itself as a tool that improves the ergonomics of the surgeon, facilitating dissection in confined spaces and enhancing the surgeon's skills. The technical aspects for successful bile duct repair are well-vascularized ducts, tension-free anastomosis, and complete drainage of hepatic segments, and all are achievable with robotic-assisted approach. METHODS: This was a retrospective study of our prospectively collected database of patients with iatrogenic bile duct injury who underwent robotic-assisted Roux-en-Y hepaticojejunostomy. Pre-, intra-, and short-term postoperative data were analyzed. RESULTS: A total of 30 consecutive patients were included. The median age was 46.5 years and 76.7% were female. Neo-confluences with section of hepatic segment IV were performed in 7 patients (those classified as Strasberg E4). In the remaining 23, a Hepp-Couinaud anastomosis was built. There were no intraoperative complications, the median estimated blood loss was 100 mL, and the median operative time was 245 min. No conversion was needed. The median length of stay was 6 days and the median length of follow-up was 8 months. The overall morbidity rate was 23.3%. Two patients presented hepaticojejunostomy leak. No mortality was registered. CONCLUSION: Robotic surgery is feasible and can be safely performed, with acceptable short-term results, in bile duct injury repair providing the advantages of minimally invasive surgery. Further studies with larger number of cases and longer follow-up are needed to establish the role of robotic assisted approaches in the reconstruction of BDI.