Effect of Herniarin on Cell Viability, Cell Cycle, and Erk Protein Levels in Different Stages of Bladder Cancer Cells.

This study examines the potential of herniarin from tarragon, as an agent with multifaceted effects on bladder cancer cells and investigates herniarin's impact on cell viability, migration, cell cycle regulation, apoptosis induction, and Erk signaling pathways in bladder cancer cell lines, including RT-112 (grade 1, non-invasive), HTB9 (grade 2, invasive), and HT1376 (grade 3, invasive), through comprehensive in vitro experiments. The compound causes cell cycle arrest at distinct phases in different cell lines: G1/S arrest in RT112 cells, G2/M arrest in HTB9 cells, and S phase arrest in HT1376 cells. Furthermore, herniarin induces caspase-mediated apoptosis in various cell lines and simultaneously modulates protein levels of apoptotic and anti-apoptotic proteins, indicating its potential as a therapeutic agent. Herniarin's influence also extends to Erk signaling, a crucial pathway that regulates cell growth and differentiation. In conclusion, this study reveals herniarin's potential as a versatile agent in the treatment of bladder cancer.

Therapeutic drug monitoring of vancomycin in the case of augmented renal clearance: a case report of a paediatric patient.

Augmented renal clearance (ARC) is a condition in which renal circulation increases, causing drug levels in the blood to remain at subtherapeutic levels in severe trauma patients. Vancomycin, a hydrophilic anti-Gram-positive drug, has been shown in the literature to have its levels fall below the therapeutic range in the case of ARC. However, vancomycin dosing recommendations in the case of ARC are still lacking. Here, we identify an ARC case measured with urinary creatinine clearance in a severe trauma paediatric patient, causing vancomycin blood trough levels to drop. We could not be able to increase the vancomycin trough levels with intermittent dosing; hence, we administered vancomycin with continuous infusion, and this resulted in vancomycin blood trough levels remaining in the therapeutic range. No adverse effect was seen. Continuous infusion of vancomycin can be safely administered to paediatric patients in these cases.

The comparison of functional status and health-related parameters in ovarian cancer survivors with healthy controls.

PURPOSE: The primary purpose of this study was to evaluate functional status and health-related parameters in ovarian cancer (OC) survivors and to compare these parameters with healthy controls. The secondary purpose of this study was to compare these parameters in early and advanced OC survivors. METHODS: Thirty-two OC survivors (n = 15 early stage; n = 17 advanced stage) with no evidence/suspicion of cancer recurrence after completing adjuvant local and systemic treatments for at least 12 months and 32 healthy controls were recruited for functional- and health-related assessments. Participants were assessed using the following methods of measuring the following: 6-min walk test (6MWT) for functional exercise capacity, 30-s chair stand test (30 s-CST) for functional fitness and muscle endurance, a handheld dynamometer for peripheral muscle strength, and a handheld dynamometer for lower extremity strength, Medical Micro RPM for respiratory muscle strength, International Physical Activity Questionnaire-Short Form (IPAQ-SF) for physical activity level, and Eastern Cooperative Oncology Group Performance Scale (ECOG-PS) for performance status, Checklist Individual Strength (CIS) for fatigue, Treatment/Gynecological Oncology-Neurotoxicity (FACT/GOG-NTX) for neuropathy, the Hospital Anxiety and Depression Scale (HADS) for anxiety and depression level, and the World Health Organization-Five Well-Being Index (WHO-5) for generic quality of life. RESULTS: All OC survivors underwent surgery and chemotherapy, and only 9.4% received radiotherapy in addition to chemotherapy. The median recurrence-free period post-completion of adjuvant treatments was 24.00 (12.00-75.00) months. OC survivors had lower 6MWT (m) (p < 0.001, r = 1.50), peripheral muscle strength (p = 0.005, r = 0.72), knee extension (p < 0.001, r = 1.54), and respiratory muscle strength (maximal inspiratory pressure) (p < 0.001, r = 1.90) (maximal expiratory pressure) (p < 0.001, r = 1.68) compared to healthy controls. HADS-A (p = 0.005, r = 0.75) and CIS scores (p = 0.025, r = 0.59) were also higher in the OC survivors. Early-stage OC survivors had better 6MWT (m) than advanced-stage OC survivors (p = 0.005, r = 1.83). Peripheral muscle strength was lower in advanced-stage OC survivors (p = 0.013, r = 0.92). FACT/GOG-NTX scores were higher in early-stage OC survivors (p < 0.001, r = 1.42). No significant differences were observed between early- and advanced-stage OC survivors in other measures (p < 0.05). CONCLUSION: The findings suggest functional status, and health-related parameters are negatively affected in OC survivors. Additionally, higher levels of fatigue, neuropathy anxiety, and depression were reported in advanced OC survivors.

Lavandula stoechas L. subsp. stoechas, a New Herbal Source for Ursolic Acid: Quantitative Analysis, Purification and Bioactivity Studies.

In this study, methanol, ethanol, methanol-dichloromethane (1 : 1, v/v), acetone, ethyl acetate, diethyl ether, and chloroform extracts of lavender (Lavandula stoechas L. subsp. stoechas) were prepared by maceration, and the ursolic acid contents in the extracts were determined quantitatively by HPLC analyses. The present results show that the methanol-dichloromethane (1 : 1, v/v) solvent system is the most efficient solvent system for the extraction of ursolic acid from the plant sample with the highest yield (2.22 g/100 g plant sample). In the present study, a new practical method for the isolation of ursolic acid from polar extracts was also demonstrated for the first time. The inhibition effects of the extracts and ursolic acid were also revealed on α-glycosidase, acetylcholinesterase, butyrylcholinesterase, and human carbonic anhydrase I and II enzymes by determining IC50 values for the first time. The extracts and ursolic acid acted as potent antidiabetic agents by strongly inhibiting the α-glycosidase activity, whereas they were found to be very weak neuroprotective agents. In view of the present results, L. stoechas and its major metabolite, ursolic acid, can be recommended as a herbal source to control postprandial blood sugar levels and prevent diabetes by delaying the digestion of starch in food.

The Mitochondrion: A Promising Target for Kidney Disease.

Mitochondrial dysfunction is important in the pathogenesis of various kidney diseases and the mitochondria potentially serve as therapeutic targets necessitating further investigation. Alterations in mitochondrial biogenesis, imbalance between fusion and fission processes leading to mitochondrial fragmentation, oxidative stress, release of cytochrome c and mitochondrial DNA resulting in apoptosis, mitophagy, and defects in energy metabolism are the key pathophysiological mechanisms underlying the role of mitochondrial dysfunction in kidney diseases. Currently, various strategies target the mitochondria to improve kidney function and kidney treatment. The agents used in these strategies can be classified as biogenesis activators, fission inhibitors, antioxidants, mPTP inhibitors, and agents which enhance mitophagy and cardiolipin-protective drugs. Several glucose-lowering drugs, such as glucagon-like peptide-1 receptor agonists (GLP-1-RA) and sodium glucose co-transporter-2 (SGLT-2) inhibitors are also known to have influences on these mechanisms. In this review, we delineate the role of mitochondrial dysfunction in kidney disease, the current mitochondria-targeting treatment options affecting the kidneys and the future role of mitochondria in kidney pathology.

A new specific method for isolation of tomentosin with a high yield from Inula viscosa (L.) and determination of its bioactivities.

INTRODUCTION: Tomentosin, the characteristic component of Inula viscosa (L.) is an important sesquiterpene lactone with anticarcinogenic effects. Methods of obtaining pure tomentosin are not sufficient for anticancer drug research. OBJECTIVES: This study aims to develop a specific method to isolate tomentosin from I. viscosa with high yield. It also aims to investigate the inhibitory effects of tomentosin on human carbonic anhydrase I (hCAI), human carbonic anhydrase II (hCAII), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glucosidase, and α-amylase enzymes. MATERIAL AND METHODS: Tomentosin was purified by a specific column chromatography method. The content of tomentosin in dichloromethane, dichloromethane by Soxhlet method, ethanol and ethanol by Soxhlet method extracts of I. viscosa was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Half maximal inhibitory concentration (IC50 ) and inhibition constant (Ki ) values were calculated to determine in vitro enzyme inhibition effects. RESULTS: Tomentosin was isolated in high yield (0.64%). The IC50 and Ki values for tomentosin were calculated as 5.00 ± 0.19 (r = 0.9688) and 4.62 ± 0.10 µM for hCAI, 5.40 ± 0.26 (r = 0.9677) and 5.22 ± 0.31 µM for hCAII, 6.75 ± 0.208 (r = 0.9891) and 3.75 ± 0.27 µM for AChE, 6.67 ± 0.307 (r = 0.9820) and 0.51 ± 0.11 µM for BChE, 26.61 ± 0.236 (r = 0.9815) and 2.61 ± 0.71 µM for α-glucosidase and 26.89 ± 1.54 µM (r = 0.9670) for α-amylase, respectively. CONCLUSION: Tomentosin was isolated in high yield from the paste-like extract of I. viscosa compared to the positive controls, it was determined that tomentosin was weakly effective against hCAI, hCAII, AChE and BChE, but thoroughly effective against α-glucosidase and α-amylase. These results suggested that tomentosin has α-glucosidase and α-amylase inhibitor potential.

Influence of Periodontitis, Implant, and Prosthesis Characteristics on the Peri-Implant Status: A Cross-Sectional Study.

BACKGROUND: The association between peri-implant diseases and the periodontal, implant, and prosthesis characteristics has been characterized in various ways. PURPOSE: The aim of this study was to evaluate the link between the peri-implant and periodontal status and the influence of implant and prosthesis parameters during implant follow-up. MATERIALS AND METHODS: One hundred and seven patients with a total of 310 implants that had at least one year of function who were attending periodontal and implant maintenance at a university clinic setting were included in this cross-sectional study. The demographic, periodontal, peri-implant tissue, implant, and prosthesis parameters were recorded. A pocket depth > 4 mm with bleeding on probing defined periodontal/peri-implant soft tissue diseased sites. Analyses were performed at the patient and implant levels using univariable and multivariable mixed regression analysis. RESULTS: The mean implant follow-up was 7.22 years. At the patient level, the bleeding on probing and pocket depth measurements were more pronounced around the implant than around the teeth. The opposite was observed for plaque and the clinical attachment levels. At the implant level, multivariable analysis showed that the periodontal and corresponding peri-implant tissue parameters, such as diseased sites, were closely related. The implant location, bone level, and number were selectively associated with the implant bone level, while cemented retention and emergence restoration profile influenced the implant pocket depth. CONCLUSIONS: The present study suggested that clinical peri-implant and periodontal soft tissue statuses were different, which could be a consequence of the initial implant and prosthesis healing process. However, during implant follow-up, the peri-implant parameters were predominantly associated with their corresponding periodontal parameters regardless of an association with the implant and prosthesis characteristics. This trial is registered with ClinicalTrials.gov ID: NCT03841656.

In vitro pharmacological screening of antioxidant, cytotoxic and enzyme inhibitory activities of Citrus aurantifolia Linn. Dried fruit extract.

The Lime Basra (Citrus aurantifolia Linn., Rutaceae) plant also known as dried lime, and Limoo Omani, is used both as a spice in meals and as an herbal tea in the treatment of some diseases in the Middle East. It was aimed to determine the biological activity screening of the 70% methanol, ethanol extracts and infusion which were prepared from dried fruits. 1,1-diphenyl-2-picrylhydrazyl (DPPH●) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS+●) radical scavenging activities, ferric reducing activity, cytotoxicity on A 549, MCF 7 and L929 cell lines and α-amylase inhibitory effects were determined. According to the results, 70% methanol extract was more active in antioxidant activity tests and ethanol extract was more active in cytotoxicity tests. Interestingly both 70% methanol and ethanol extracts were found to have potent hypoglycemic activity. The present findings shed light on the fact that it is important to research and scientifically evaluate plants with traditional medicinal use.

human monoamine oxidase (hMAO) A and hMAO B inhibitors from Artemisia dracunculus L. herniarin and skimmin: human mononamine oxidase A and B inhibitors from A. dracunculus L.

The aim of this study was to investigate the effects of extracts and pure Artemisia dracunculus L. (tarragon) metabolites on the antimonoamine oxidase and anticholinesterase activities. The compounds were characterized as stigmasterol (1), herniarin (2), (2E,4E)-1-(piperidin-1-yl)undeca-2,4-diene-8,10-diyn-1-one (3), (2E,4E)-N-isobutylundeca-2,4-dien-8,10-diynamide (4), 3,4-dehydroherniarin (5) and skimmin (6) by 1H-NMR, 13C-NMR, 1D and 2D NMR methods. The compounds 5 and 6 were isolated from tarragon for the first time. The extracts and pure compounds have inhibitory effects on the human monoamine oxidase (hMAO) A and B enzymes, whereas they did not exhibit any anticholinesterase activities. Among the tarragon compounds, only 2 and 6 compounds showed the inhibitory effects against hMAO A (IC50 = 51.76 and 73.47 µM, respectively) and hMAO B (IC50 = 0.84 and 1.63 mM, respectively). In the study, herniarin content in the extracts was also analysed by high-performance liquid chromatography and it was found that there was a relationship between the inhibition effects of the extracts and their herniarin content.

Antihemorrhoidal activity of organic acids of Capsella bursa-pastoris on croton oil-induced hemorrhoid in rats.

This study was aimed to investigate the antihemorrhoidal effects of ethanol (CBE) and water extracts (CBW) of Capsella bursa-pastoris, an edible plant and a precipitant (CBW-1) obtained from the CBW in croton oil (CO)-induced hemorrhoid model in rats. CBW-1 was contain three organic acids, citric acid (36.09%), malic acid (35.56%), and quinic acid (17.73%). Hemorrhoids were evaluated by histopathology of recto-anal tissues and biochemical parameters in plasma and recto-anal tissues of rats. CBW, CBE, and CBW-1 significantly reduced hemorrhagic necrotic enteritis induced by CO. CO also increased the cytokines and lipid peroxidation (LPO) in serum, and myeloperoxidase (MPO) activity and LPO in recto-anal tissues, and reduced the GSH, CAT, GPx, and SOD levels in serum and recto-anal tissues. However, CBE, CBW, and CBW-1 ameliorated the levels of the cytokines, LPO, MPO, and the antioxidants. Our results conclude that the curative effect of Capsella bursa-pastoris is closely related with its organic acids constituents, citric, malic, and quinic acids. PRACTICAL APPLICATIONS: The fresh leaves of Capsella bursa-pastoris are edible, eaten raw or cooked, and also used in salad. It has a widespread traditional usage in the treatment of the hemorrhoids in the Anatolia and in the Middle East Countries. According to our literature survey, any scientific evidence has not been found in the literature that C. bursa-pastoris could be used in the treatment of hemorrhoids. Therefore, in the current study, we aimed to investigate the antihemorrhoidal and antioxidant effects of ethanol and water extracts, and a precipitant (CBW-1) obtained from the CBW of C. bursa-pastoris in croton oil (CO)-induced hemorrhoid model in rats. The current results showed that its water extract and CBW-1 containing three organic acids, citric acid (36.09%), malic acid (35.56%), and quinic acid (17.73%) significantly reduced the hemorrhagic necrotic enteritis induced by CO ameliorating the levels of the cytokines, LPO, MPO, and the antioxidants. Our results conclude that the curative effect of C. bursa-pastoris is closely related with its organic acids constituents, citric, malic, and quinic acids.

Protective effect of oleuropein on ketamine-induced cardiotoxicity in rats.

The antioxidant and cardioprotective effects of oleuropein have been reported in several studies; however, its effect on ketamine cardiotoxicity has not been known yet. The aim of this study was to investigate the effects of oleuropein in ketamine-induced cardiotoxicity model in rats. A total of 28 male Wistar Albino rats were included in the study and they were randomly divided into four groups, each having seven rats. Group 1 (control): rats were given 1 mL of DMSO by oral gavage method for 7 days. Group 2 (ketamine): on the seventh day of the study, 60 mg/kg ketamine was administered intraperitoneally. Then, 60 mg/kg ketamine was administered intraperitoneally every 10 min for 3 h. Group 3 (oleuropein): rats were given 200 mg/kg/day oleuropein by oral gavage method for 7 days. Group 4 (oleuropein + ketamine): rats were given 1 × 200 mg/kg oleuropein by oral gavage method for 7 days. Furthermore, 60 mg/kg ketamine was administered intraperitoneally on the seventh day of the experiment. Then, 60 mg/kg ketamine was administered intraperitoneally every 10 min for 3 h. Serum cardiac marker (TnI, CK-MB and CK) levels were measured. Histopathological analysis was performed on a portion of the cardiac tissue. Cardiac tissue oxidative stress and antioxidant markers (MDA, GSH, GSH.Px and CAT), TNF-α, IL-6, NF-κB, COX-2 and Nrf-2 gene expressions, and protein conversion levels of related genes were determined. Data obtained showed that ketamine administration increased MDA (p < 0.001), TNF-α (p < 0.01), IL-6 (p < 0.01), COX-2 (p < 0.001) and NF-κB (p < 0.001) levels, as well as serum TnI (p < 0.001), CK-MB (p < 0.001) and CK (p < 0.01) levels whereas decreased GSH (p < 0.05) and Nrf-2 (p < 0.05) levels, as well as GSH-Px (p < 0.001) and CAT (p < 0.05) enzyme activities. Oleuropein administration was observed to decrease MDA, TNF-α, IL-6, COX-2, NF-κB, TnI, CK-MB and CK levels close to the control group and to increase GSH levels and GSH-Px and CAT enzyme activities close to the control group. This study showed that oleuropein administration reversed the increased oxidative stress and inflammation as a result of the use of ketamine and had protective effects on the heart.

Auditory Nerve Fiber Health Estimation Using Patient Specific Cochlear Implant Stimulation Models.

Cochlear implants (CIs) restore hearing using an array of electrodes implanted in the cochlea to directly stimulate auditory nerve fibers (ANFs). Hearing outcomes with CIs are dependent on the health of the ANFs. In this research, we developed an approach to estimate the health of ANFs using patient-customized, image-based computational models of CI stimulation. Our stimulation models build on a previous model-based solution to estimate the intra-cochlear electric field (EF) created by the CI. Herein, we propose to use the estimated EF to drive ANF models representing 75 nerve bundles along the length of the cochlea. We propose a method to detect the neural health of the ANF models by optimizing neural health parameters to minimize the sum of squared differences between simulated and the physiological measurements available via patients' CIs. The resulting health parameters provide an estimate of the health of ANF bundles. Experiments with 8 subjects show promising model prediction accuracy, with excellent agreement between neural stimulation responses that are clinically measured and those that are predicted by our parameter optimized models. These results suggest our modeling approach may provide an accurate estimation of ANF health for CI users.

The protective role of jervine against radiation-induced gastrointestinal toxicity.

In this study, we investigated whether jervine (J) could prevent gastrointestinal (GI) side effects of abdominopelvic radiotherapy (RT) in Wistar-Albino female rats. Rats were divided into five groups: control (C), J only (J), J administered at 5 mg/kg/days for 7 days, RT only (RT), J before RT (J + RT), J administered for seven days before RT, J both before and after RT (J + RT + J), and J administered for 7 days before RT and after RT for 3 days. The weights of rats were measured on the 1st, 7th, and 10th days of the study. Rats were sacrificed to obtain tissues from the liver and intestine, which was followed by taking blood samples intracardially. In addition, the tissues were stained with pyruvate dehydrogenase (PDH) immunohistochemically. In our study, J supplementation markedly reduced weight loss, and histopathological, immunohistochemical, biochemical results suggest that J had a protective effect on GI toxicity following RT.

Anti-inflammatory and antioxidant properties of jervine, a sterodial alkaloid from rhizomes of Veratrum album.

BACKGROUND: Veratrum, hellebore is an important plant species of the Liliaceae family and jervine is the characteristic steroidal alkaloid constituent of Veratrum album. PURPOSE: In the current study, anti-inflammatory and antioxidant effects of jervine isolated from NH4OH-benzene extract of V. album rhizomes were investigated on CAR induced paw edema in rats. METHODS/STUDY DESIGN: In inflammatory study, 50, 100, 200 and 400  mg/kg doses of jervine, 25  mg/kg doses of DIC and IND were orally administered, and the volume of the foots were measured up to their knee arthrosis by plethismometer. After one hour of the oral administration of the all treatments, 0.1 ml of CAR solution (1%) was injected into the foot of the all rat groups and the volume of the foots were measured during 5 h after CAR injection. GPx, SOD, GR, MPO, CAT enzymes activities and GSH, LPO levels of the supernatants of paw homogenates and inflammation biomarkers such as TNF-α and IL-1ß in the rats serums were also estimated. RESULTS: According to the present results, jervine exerted 50.4-73.5% anti-inflammatory effects in carrageenan induced paw edema. Inflammation biomarkers such as TNF-α, IL-1ß and MPO that increased by CAR injection were suppressed by the administrations of all doses of jervine, IND and DIC. In all paw tissues, LPO levels as indicator of oxidative tissue damage were found to be high in CAR-treated group and it was found to be decreased in all doses of jervine. CONCLUSION: Jervine, DIC and IND reduced the negative effects of CAR due to increasing effects on the SOD, CAT, GSH, GPx and GR antioxidants.

Short-term outcomes of outpatient surgery for total knee arthroplasty.

INTRODUCTION: We developed an accelerated clinical pathway involving outpatient surgery for patients undergoing total knee arthroplasty (TKA) who are healthy enough for early discharge. METHODS: Between March 2014 and April 2015, 89 TKAs were performed at a single institution by a single orthopaedic surgeon. 31 patients met the inclusion criteria for the study. All patients received 2 g tranexamic acid and 750 mg cefuroxime sodium intravenously 30 minutes prior to surgery. A multimodal protocol for perioperative pain management was used for all patients. RESULTS: 31 patients (three male, 28 female), with a mean age of 67 (range 49-78) years, who underwent TKA were enrolled in this study. The mean length of hospital stay was 28.7 (range 16-49) hours and mean duration of surgery was 92 (range 75-128) minutes. Combined spinal epidural anaesthesia was performed for 23 (74.2%) patients and general anaesthesia was used in 8 (25.8%) patients. Among the 31 patients, 23 (74.2%) patients were discharged within 23 hours of surgery. CONCLUSION: Early discharge of patients following outpatient surgery for TKA was not associated with any procedure-related complications among the selected patients up to three months postoperatively.

Evaluation of a high-resolution patient-specific model of the electrically stimulated cochlea.

Cochlear implants (CIs) are surgically implanted medical devices used to treat individuals with severe-to-profound sensorineural hearing loss. Although these devices have been remarkably successful at restoring audibility, many patients experience poor outcomes. Our group has developed the first image-guided CI programming technique where the electrode positions are found in CT images and used to estimate neural activation patterns, which is unique information that audiologists can use to define patient-specific processor settings. Currently, neural activation is estimated using only the distance from each electrode to the neural activation sites, which might be less accurate than using high-resolution electro-anatomical models (EAMs) to perform physics-based estimations of neural activation. We propose a patient-customized EAM approach where the EAM is spatially and electrically adapted to a patient-specific configuration. Spatial adaptation is done through nonrigid registration of the model with the patient CT image. Electrical adaptation is done by adjusting tissue resistivity parameters, so the intracochlear voltage distributions predicted by the model best match those directly measured for the patient via their implant. We found that our approach, demonstrated for [Formula: see text] patients, results in mean percent differences between direct and simulated measurements of voltage distributions of 10.9%.

Magnetic resonance imaging connectivity for the prediction of seizure outcome in temporal lobe epilepsy.

OBJECTIVE: Currently, approximately 60-70% of patients with unilateral temporal lobe epilepsy (TLE) remain seizure-free 3 years after surgery. The goal of this work was to develop a presurgical connectivity-based biomarker to identify those patients who will have an unfavorable seizure outcome 1-year postsurgery. METHODS: Resting-state functional and diffusion-weighted 3T magnetic resonance imaging (MRI) was acquired from 22 unilateral (15 right, 7 left) patients with TLE and 35 healthy controls. A seizure propagation network was identified including ipsilateral (to seizure focus) and contralateral hippocampus, thalamus, and insula, with bilateral midcingulate and precuneus. Between each pair of regions, functional connectivity based on correlations of low frequency functional MRI signals, and structural connectivity based on streamline density of diffusion MRI data were computed and transformed to metrics related to healthy controls of the same age. RESULTS: A consistent connectivity pattern representing the network expected in patients with seizure-free outcome was identified using eight patients who were seizure-free at 1-year postsurgery. The hypothesis that increased similarity to the model would be associated with better seizure outcome was tested in 14 other patients (Engel class IA, seizure-free: n = 5; Engel class IB-II, favorable: n = 4; Engel class III-IV, unfavorable: n = 5) using two similarity metrics: Pearson correlation and Euclidean distance. The seizure-free connectivity model successfully separated all the patients with unfavorable outcome from the seizure-free and favorable outcome patients (p = 0.0005, two-tailed Fisher's exact test) through the combination of the two similarity metrics with 100% accuracy. No other clinical and demographic predictors were successful in this regard. SIGNIFICANCE: This work introduces a methodologic framework to assess individual patients, and demonstrates the ability to use network connectivity as a potential clinical tool for epilepsy surgery outcome prediction after more comprehensive validation.

Natural product inhibitors of carbonic anhydrase I and II isoenzymes: osajin and pomiferin.

The aim of this study is to purify carbonic anhydrase I and II isoenzymes from human erythrocyte, isolate two natural products osajin (OSJ) and pomiferin (PMF) from Maclura pomifera fruits, and evaluate the in vitro effect of these natural metabolites on these isoenzymes. These natural products may be used as starting points for drug discovery (like drugs used in several therapeutic applications, including antiglaucoma activity). For the purification procedure, the Sepharose-4B-l-tyrosine-sulphonamide affinity chromatography was used. Column chromatography and thin layer chromatography methods were used for isolation of OSJ and PMF from M. pomifera fruits and their chemical structures were elucidated by IR, 1D, and 2D NMR methods. We compared inhibitory effects of these natural products with inhibitory effects of phenolic compounds and found that these products demonstrated average inhibition effects. We thought that this study will give inspiration to scientists interested in this issue.

Automatic Cochlear Duct Length Estimation for Selection of Cochlear Implant Electrode Arrays.

HYPOTHESIS: Cochlear duct length (CDL) can be automatically measured for custom selection of cochlear implant (CI) electrode arrays. BACKGROUND: CI electrode array selection can be influenced by measuring the CDL, which is estimated based on the length of the line that connects the round window and the lateral wall of the cochlea when passing through the modiolus. CDL measurement remains time consuming and inter-observer variability has not been studied. METHODS: We evaluate an automatic approach to directly measure the two-turn (2T) CDL using existing algorithms for localizing cochlear anatomy in computed tomography (CT). Pre-op CT images of 309 ears were evaluated. Two fellowship-trained neurotologists manually and independently measured CDL. Inter-observer variability between measurements across expert and automatic observers is assessed. Inter-observer differences for choice of electrode type are also investigated. RESULTS: Manual measurement of CDL by experts tends to underestimate cochlea size and has high inter-observer variability, with mean absolute differences between expert CDL estimations of 1.15 mm. Our results show that this can lead to a large number of cochleae for which a different electrode array type would be selected by different observers, depending on the specific threshold value of CDL used to decide between array type. CONCLUSION: Choosing the best CI electrode array is an important task for optimizing hearing outcomes. Manual cochleae length measurements are user-dependent, and errors impact upon the CI electrode array choice for certain patients. Measuring cochlea length automatically is less time consuming and generates more repeatable results. Our automatic approach could make use of CDL for patient-customized treatment more clinically adoptable.