Intermediate cells in normal and malignant prostate epithelium express c-MET: implications for prostate cancer invasion.
Analysis of keratin (K) expression discriminates luminal (K18) and intermediate (K5/18) cells in prostate carcinoma, while basal (K5/14) cells are absent. Intermediate cells have been proposed as targets of malignant transformation in prostate cancer and precursors of androgen-independent tumor progression. We demonstrate localization of hepatocyte growth factor (HGF) receptor c-MET in intermediate cells in both normal and malignant prostate epithelium. Receptor localization was analyzed using triple staining for c-MET, K5, K14, and K18. The percentage of strongly c-MET positive cells was determined in 15 prostate cancer patients undergoing androgen-deprivation and 14 patients without neo-adjuvant treatment. Effects of HGF were investigated on prostate cancer cell line DU145. c-MET expression in non-malignant epithelium was strong in intermediate cells absent in differentiated cells, and heterogeneous in basal cells. In prostate cancer, intermediate cells displayed high c-MET levels coupled with mild expression in differentiated cells. During androgen-deprivation, 7.6% of tumor cells revealed high c-MET expression compared to 1.7% without treatment (P = 0.02). Matrigel penetration of DU145 was 8.2 +/- 1.7 mm(2) after HGF stimulation compared to 3.6 +/- 2.4 mm(2) in controls (P < 0.02). Intermediate cells in normal and malignant prostate epithelium express high c-MET levels, indicating that they are prone to stromal invasion in prostate carcinoma.


Prevention of myocardial depression in experimental hemorrhagic shock by pretreatment with hydrocortisone.
The left anterior descending or left circumflex coronary artery was cannulated in ten dogs. 4 mg/kg hydrocortisone were slowly infused and the cannula was withdrawn. The dogs were then subjected to hemorrhagic shock for 90 minutes followed by retransfusion. The contractile force (CF) and its first derivative (df/dt) were measured in the pretreated (infused) area and in a control (non-perfused) area of the left ventricle. During the shock period, CF and df/dt in the non-pretreated area showed a 50% reduction in comparison to the pre-shock level, whereas the contractile force in the area that had been pretreated with hydrocortisone did not change when compared to the pre-shock period. This study shows that myocardial depression secondary to hemorrhagic shock can be effectively prevented by pretreatment with hydrocortisone.


A population-coding model of attention's influence on contrast response: Estimating neural effects from psychophysical data.
Human psychophysics and monkey physiology studies have shown that attention modulates early vision - contrast sensitivity and processing. But how can we bridge the effects of attention on perceptual performance to their neural underpinnings? Here we implement a population-coding model that estimates attentional effects on population contrast response given psychophysical data. Model results show that whereas endogenous (sustained, voluntary) attention changes population contrast-response via contrast gain, exogenous (transient, involuntary) attention changes population contrast-response via response gain.


Stable solution of the simplest spin model for inverse freezing.
We analyze the Blume-Emery-Griffiths-Capel model with disordered interaction that displays the inverse freezing phenomenon. The behavior of this spin-1 model in crystal field is studied throughout the phase diagram, and the transition lines are computed using the full replica symmetry breaking ansatz. We compare the results both with the formulation of the same model in terms of Ising spins on lattice gas, where no reentrance takes place, and with the model with generalized spin variables recently introduced by Schupper and Shnerb [Phys. Rev. Lett. 93, 037202 (2004)], for which the reentrance is enhanced as the ratio between the degeneracy of full to empty sites increases. The simplest version of all these models, known as the Ghatak-Sherrington model, turns out to hold all the general features characterizing an inverse transition to an amorphous phase.


Direct and indirect action modes of acetylcholine in cholinergic urticaria.
Cholinergic urticaria (CholU) manifests small, itchy and/or painful wheals occurring upon perspiration and mechanically involving acetylcholine (Ach). Although a considerable number of studies have been conducted, the pathomechanisms underlying perspiration-associated release of histamine remain to be elucidated. We have proposed that CholU can be categorized into two major subtypes: Ach-indirectly induced, sweat allergic type and Ach-directly induced, depressed sweating type. In the former type, Ach evokes perspiration, and some sweat antigen(s) leaking from the sweat ducts to the dermis may stimulate mast cells to release histamine. In this scenario, the ducts might be damaged or obstructed for sweat leakage, and patients frequently exhibit positive autologous sweat skin test, representing "sweat allergy (hypersensitivity)". On the other hand, the latter Ach-mast cell directly interacting type, typically seen as "CholU with anhidrosis and/or hypohidrosis (CUAH)", eccrine sweat gland epithelial cells lack cholinergic receptor M3 expression. The expression of cholinergic receptors is completely absent in the anhidrotic areas and only slightly expressed in the hypohidrotic areas. In the hypohidrotic area, where pinpoint wheal occurs, it is hypothesized that released Ach cannot be completely trapped by cholinergic receptors of eccrine glands and overflows to the adjacent mast cells, leading to wheal formation. Thus, sweat allergy is not a requirement in this depressed sweating type. Although some additional complications, such as angioedema, anaphylaxis, and cold urticaria, have been documented, these two types represent the modes of action of Ach in this enigmatic urticaria.


Potential role of allopregnanolone for a safe and effective therapy of neuropathic pain.
Because the treatment and management of neuropathic pain are extremely complicated, the characterization of novel analgesics and neuroprotectors with safe toxicological profiles is a crucial need to develop efficient therapies. Several investigations revealed that the natural neurosteroid allopregnanolone (AP) exerts analgesic, neuroprotective, antidepressant and anxiolytic effects. These effects result from AP ability to modulate GABA(A), glycine, L- and T-type calcium channels. It has been shown that AP treatment induced beneficial actions in humans and animal models with no toxic side effects. In particular, a multi-parametric analysis revealed that AP efficiently counteracted chemotherapy-evoked neuropathic pain in rats. It has also been demonstrated that the modulation of AP-producing enzyme, 3α-hydroxysteroid oxido-reductase (3α-HSOR), in the spinal cord regulates thermal and mechanical pain thresholds of peripheral nerve injured neuropathic rats. The painful symptoms were exacerbated by intrathecal injections of provera (pharmacological inhibitor of 3α-HSOR) which decreased AP production in the spinal cord. By contrast, the enhancement of AP concentration in the intrathecal space induced analgesia and suppression of neuropathic symptoms. Moreover, in vivo siRNA-knockdown of 3α-HSOR expression in healthy rat dorsal root ganglia increased thermal and mechanical pain perceptions while AP evoked a potent antinociceptive action. In humans, blood levels of AP were inversely associated with low back and chest pain. Furthermore, oral administration of AP analogs induced antinociception. Altogether, these data indicate that AP, which possesses a high therapeutic potential and a good toxicological profile, may be used to develop effective and safe strategies against chronic neuropathic pain.


MTDH and EphA7 are markers for metastasis and poor prognosis of gallbladder adenocarcinoma.
Gallbladder cancer is an aggressive cancer with extremely poor prognosis. Over 90% of patients are diagnosed at an advanced, inoperable stage with metastasis and invasion to other organs. In this study, the expression of metadherin (MTDH) and erythropoietin-producing hepatoma-amplified sequence (Eph) receptor A7 (EphA7) in 96 benign and 108 malignant lesions of gallbladder was determined by immunohistochemistry, and their correlations with pathological features and prognosis were analyzed. Positive expression of EphA7 and MTDH was significantly higher in gallbladder adenocarcinoma than in benign lesions. In adenocarcinoma, the positive expression of EphA7 and MTDH was significantly associated with differentiation, tumor mass, lymphnode metastasis, invasion, and overall survival. Multivariate Cox regression analysis suggested that positive expression of EphA7 and MTDH was an independent poor-prognostic predictor in gallbladder adenocarcinoma. The elevated expression of EphA7 and/or MTDH is closely related to carcinogenesis, progression, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.


New Keystone flap application in vulvo-perineal reconstructive surgery: A case series.
This study aimed to evaluate the application of the Keystone flap technique and the long-term results of vulvovaginal reconstruction after vulvar surgery. This is the first case series describing the application of the Keystone perforator island flaps (KPIF) technique to close a wide defect after radical vulvectomy. We prospectively collected patient demographics, operative times, complications, pathologic results, and length of stay on all patients. The benefits, cosmetic results and satisfaction of patients were analyzed in the follow up. Five patients were selected for the study: four underwent radical vulvectomy for squamous cell vulvar cancer, and one underwent vulvar wide excision for Paget disease followed by reconstruction with the Keystone flap technique. The defects were successfully covered by the Keystone flap technique in all patients. Keystone flaps seem to be easy to design and elevate, and it offers rapid fasciocutaneous closure in wide vulvo-perineal defects with excellent long-term results.


Increased expression of transforming growth factor-alpha in a patient with recurrent hepatocellular carcinoma following partial hepatectomy.
A 45-year-old woman with chronic hepatitis B underwent partial hepatectomy for hepatocellular carcinoma (HCC). However, the HCC recurred 2 months after surgery and rapid progression of the disease resulted in her death. Immunohistochemistry showed that transforming growth factor-alpha (TGFalpha) was barely expressed in the liver specimens obtained at hepatic resection, whereas autopsy specimens were strongly stained with anti-TGFalpha antibody in the cytoplasm of both non-tumourous and tumourous liver cells. A higher level of Ki67 expression, a proliferating marker, was observed in the recurrent HCC, similar to that of TGFalpha. Thus, we speculate that the partial hepatectomy increased the level of TGFalpha leading to recurrence and progression of HCC through an autocrine/paracrine mechanism.


Variations in Case-Mix-Adjusted Duration of Mechanical Ventilation Among ICUs.
To develop a model that predicts the duration of mechanical ventilation and then to use this model to compare observed versus expected duration of mechanical ventilation across ICUs. Retrospective cohort analysis. Eighty-six eligible ICUs at 48 U.S. hospitals. ICU patients receiving mechanical ventilation on day 1 (n = 56,336) admitted from January 2013 to September 2014. None. We developed and validated a multivariable logistic regression model for predicting duration of mechanical ventilation using ICU day 1 patient characteristics. Mean observed minus expected duration of mechanical ventilation was then obtained across patients and for each ICU. The accuracy of the model was assessed using R. We defined better performing units as ICUs that had an observed minus expected duration of mechanical ventilation less than -0.5 days and a p value of less than 0.01; and poorer performing units as ICUs with an observed minus expected duration of mechanical ventilation greater than +0.5 days and a p value of less than 0.01. The factors accounting for the majority of the model's explanatory power were diagnosis (71%) and physiologic abnormalities (24%). For individual patients, the difference between observed and mean predicted duration of mechanical ventilation was 3.3 hours (95% CI, 2.8-3.9) with R equal to 21.6%. The mean observed minus expected duration of mechanical ventilation across ICUs was 3.8 hours (95% CI, 2.1-5.5), with R equal to 69.9%. Among the 86 ICUs, 66 (76.7%) had an observed mean mechanical ventilation duration that was within 0.5 days of predicted. Five ICUs had significantly (p < 0.01) poorer performance (observed minus expected duration of mechanical ventilation, > 0.5 d) and 14 ICUs significantly (p < 0.01) better performance (observed minus expected duration of mechanical ventilation, < -0.5 d). Comparison of observed and case-mix-adjusted predicted duration of mechanical ventilation can accurately assess and compare duration of mechanical ventilation across ICUs, but cannot accurately predict an individual patient's mechanical ventilation duration. There are substantial differences in duration of mechanical ventilation across ICU and their association with unit practices and processes of care warrants examination.


Determination of the antitumor agent depsipeptide in plasma by liquid chromatography on serial octadecyl stationary phases.
A high-performance liquid chromatographic assay has been developed and validated for the determination of the antitumor agent depsipeptide (FR-901228) in plasma samples from patients with advanced cancer. After the plasma proteins were precipitated with acetonitrile, the supernatant was extracted with ethylacetate. Depsipeptide was chromatographed on two serial octadecylsilica stationary phases using a mobile phase consisting of acetonitrile-potassium phosphate buffer (0.03 M, pH 3) (27:73, v/v), at a flow-rate of 2.0 ml/min and at ambient temperature. The method was linear over a 50 to 2000 ng/ml range and the intra- and inter-day coefficients of variations were less than 8%. The method was applied to the determination of the plasma concentration-time profile for 14 patients with advanced cancer receiving from 1 to 7.5 mg/m2 of depsipeptide per day as a continuous 4-h infusion.


[Diagnosis of spinal cord tumor in pediatric orthopedics].
The clinical findings leading to the diagnosis of a spinal cord tumor in pediatric orthopedics are reported with a discussion of the neuro-urological aspects.


What makes the cell differentiate?
In the present paper, I propose a hypothesis whereby the necessity to maintain the permanent energy-dissipating metabolic flux represents the primary force that determines the eukaryotic cell's choice to grow, divide and/or differentiate. This view is based on the universal structure and the strict redox neutrality of the core metabolic network. I propose that the direct substrate level coupling between metabolism and gene expression through epigenetic mechanisms provides a mechanistic explanation of how this control is implemented.


Association between severe periodontitis and chronic kidney disease severity in predialytic patients: A cross-sectional study.
The aim of this cross-sectional study was to evaluate the association between periodontitis and different severities of chronic kidney disease (CKD) in predialytic patients. Demographic, socioeconomic, and medical data of 139 patients from the nephrology service of one university hospital in Porto Alegre, Brazil, were obtained through interview and clinical records. Full-mouth six-sites per tooth periodontal examinations were performed. Associations between periodontitis, stages of CKD, and estimated glomerular filtration rate (eGFR) were estimated by multivariable models adjusted for sex, smoking, vitamin D supplementation, physical activity, and renal treatment duration. CKD was classified based on eGFR (<60 ml/min/1.73 m2 ) estimated by the Chronic Kidney Disease Epidemiology Collaboration equation. Patients with severe periodontitis, compared to those without severe periodontitis, had 2.8 (95% CI: 1.25-6.62) and 3.4 (95% CI: 1.27-9.09) times higher risk of being in stages 4 and 5 of CKD, respectively. Having ≥ 2 teeth with clinical attachment loss (CAL) ≥6 mm increased 3.9 times the risk of being in stage 5 of CKD. Patients with severe periodontitis and ≥2 teeth with CAL ≥ 6 mm had 4.4 ml/min/1.732 and 5.2 ml/min/1.732 lower eGFR (p-values < .05), respectively. Severe periodontitis was associated with poor renal conditions in predialytic CKD patients, strengthening the importance of periodontal evaluation in such patient population.


Nebulized furosemide for the management of dyspnea: does the evidence support its use?
Dyspnea is a common and distressing symptom associated with multiple chronic illnesses and high levels of burden for individuals, their families and health care systems. The subjective nature dyspnea and a poor understanding of pathophysiological mechanisms challenge the clinician in developing management plans. Nebulized furosemide has been identified as a novel approach to dyspnea management. This review summarizes published studies, both clinical and experimental, reporting the use of nebulized furosemide. The search criteria yielded 42 articles published in the period 1988 to 2004. Although nebulized furosemide appeared to have a positive influence on dyspnea and physiological measurements, caution must be taken with the results primarily coming from small-scale clinical trials or observation trials. Despite the limitations of the studies reported, given the range of conditions reporting effectiveness of nebulized furosemide, further investigation of this potential novel treatment of dyspnea is warranted.


Distinct Functions of the Atypical Terminal Hydrophilic Domain of the HKT Transporter in the Liverwort Marchantia polymorpha.
K+/Na+ homeostasis is important for land plants, particularly under salt stress. In this study, the structure and ion transport properties of the high-affinity K+ transporter (HKT) of the liverwort Marchantia polymorpha were investigated. Only one HKT gene, MpHKT1, was identified in the genome of M. polymorpha. Phylogenetic analysis of HKT proteins revealed that non-seed plants possess HKTs grouped into a clade independent of the other two clades including HKTs of angiosperms. A distinct long hydrophilic domain was found in the C-terminus of MpHKT1. Complementary DNA (cDNA) of truncated MpHKT1 (t-MpHKT1) encoding the MpHKT_Δ596-812 protein was used to examine the functions of the C-terminal domain. Both MpHKT1 transporters fused with enhanced green fluorescent protein at the N-terminus were localized to the plasma membrane when expressed in rice protoplasts. Two-electrode voltage clamp experiments using Xenopus laevis oocytes indicated that MpHKT1 mediated the transport of monovalent alkali cations with higher selectivity for Na+ and K+, but truncation of the C-terminal domain significantly reduced the transport activity with a decrease in the Na+ permeability. Overexpression of MpHKT1 or t-MpHKT1 in M. polymorpha conferred accumulation of higher Na+ levels and showed higher Na+ uptake rates, compared to those of wild-type plants; however, phenotypes with t-MpHKT1 were consistently weaker than those with MpHKT1. Together, these findings suggest that the hydrophilic C-terminal domain plays a unique role in the regulation of transport activity and ion selectivity of MpHKT1.


Surgical therapy of congenital distal urethral stenoses in girls by meatoplasty.
In girls there are three distinct morphological kinds of congenital distal urethral stenoses in the broad sense. Incomplete meatal stenoses are the most frequent of these. Calibration of the urethra appeared to be the most reliable diagnostic tool in revealing distal urethral obstructions. To relieve the urodynamically interfering urethral stenoses we developed a resecting surgical technique. In a retrospective study the follow-up after meatoplasty of 163 girls with recurrent urinary tract infections was analysed. The long-term success rate totals up to 83.5%.


Redundancy, isomorphism, and propagative mechanisms between emotional and amodal representations of words: A computational study.
Some proposals claim that language acts as a link to propagate emotional and other modal information. Thus, there is an eminently amodal path of emotional propagation in the mental lexicon. Following these proposals, we present a computational model that emulates a linking mechanism (mapping function) between emotional and amodal representations of words using vector space models, emotional feature-based models, and neural networks. We analyzed three central concepts within the embodiment debate (redundancy, isomorphism, and propagative mechanisms) comparing two alternative hypotheses: semantic neighborhood hypothesis versus specific dimensionality hypothesis. Univariate and multivariate neural networks were trained for dimensional (N = 11,357) and discrete emotions (N = 2,266), and later we analyzed its predictions in a test set (N = 4,167 and N = 875, respectively). We showed how this computational model could propagate emotional responses to words without a direct emotional experience via amodal propagation, but no direct relations were found between emotional rates and amodal distances. Thereby, we found that there were clear redundancy and propagative mechanisms, but no isomorphism should be assumed. Results suggested that it was necessary to establish complex links to go beyond amodal distances of vector spaces. In this way, although the emotional rates of semantic neighborhoods could predict the emotional rates of target words, the mapping function of specific amodal features seemed to simulate emotional responses better. Thus, both hypotheses would not be mutually exclusive. We also showed that discrete emotions could have simpler relations between modal and amodal representations than dimensional emotions. All these results and their theoretical implications are discussed.


Beyond Ashworth. Electrophysiologic quantification of spasticity.
Spasticity is a hallmark of upper motor neuron lesion, which is easily identified but is difficult to quantify and treat. The Ashworth scale lacks reliability. Available biomechanical and electrophysiologic studies offer a more reliable measure of spastic hypertonia but have limited clinical utility. A uniformly acceptable, reliable, and practical measure of spasticity continues to elude the clinician. This chapter reviews the basic neuroanatomy and physiology of the stretch reflex and the pathophysiology of the spasticity. Current biomechanical and electrophysiological techniques are used to quantify spasticity.


[A comparative hormonal and clinical analysis of thyrotoxicosis with- or without comorbid resistant depression].
To compare clinical and hormonal status in thyrotoxicosis with- or without comorbid resistant depression. We examined 100 patients with thyrotoxicosis, including 61 patients with comorbid resistant depression (RD) and 39 patients without RD. Mental status, somatic symptoms of disease and blood content of main thyroid hormones were studied. The Hamilton scale was used to measure depression and anxiety. Depression developed in the structure of thyrotoxicosis increased the symptoms of hyperthyroidism. However, it did not change the general tendency of development of the main disease assessed by hormonal indicators.


Surgical Fixation of Geriatric Sacral U-Type Insufficiency Fractures: A Retrospective Analysis.
To define the incidence of sacral U-type insufficiency fracture and describe management of a consecutive series of patients with this injury. Retrospective analysis. Single Level II trauma center. Sixteen adult patients with sacral U-type insufficiency fractures treated over a 36-month period. Patients were indicated for percutaneous screw fixation of the posterior pelvis if they had posterior pelvic pain that prohibited mobilization. Visual analog scale for pain, distance ambulated on postoperative day 1, and change in sacral kyphosis. The sacral U-type insufficiency fracture incidence was 16.7% (19/114); average patient age was 75 years. Delayed surgery was performed after primary nonoperative treatment had failed in 62.5% (10/16) at an average 83 days postinjury. Acute surgery was performed in 37.5% (6/16) at an average 5 days postinjury. Distance ambulated on postoperative day 1 was 114.4 feet [95% confidence interval (CI) (50.6, 178.2)] and 88.7 feet [95% CI (2.8, 174.6)] in the delayed and acute surgery groups, respectively, P = 0.18. Change in visual analog scale for pain was -3.2 [95% CI (-5.0, -1.4)] and -3.7 [95% CI (-7.0, -0.4)] in the delayed and acute surgery groups, respectively, P = 0.15. Change in sacral kyphosis from presentation to surgery was 12.3 degrees [95% CI (6.7, 17.9)] and 0.3 degrees [95% CI (-0.2, 0.9)] in the delayed and acute surgery groups, respectively, P < 0.01. Minimum follow-up was 12 months. Treatment of sacral U-type insufficiency fractures by percutaneous screw fixation permits early mobilization, provides rapid pain relief, and prevents progressive deformity. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


A feasibility study on biweekly administration of docetaxel for patients with recurrent ovarian cancer.
A recent study demonstrated that docetaxel (DTX) was an effective agent for second line chemotherapy against ovarian cancer. Weekly administration of taxane compounds had been more effective compared with a 3 week interval administration in ovarian cancer. The role of biweekly administration of DTX has been unknown. We conducted a dose determination and feasibility study of biweekly DTX administration in patients with ovarian cancer. Patients with histologically confirmed epithelial ovarian cancer who received one or more regimens of prior chemotherapy with more than 4 weeks of treatment-free interval were eligible. DTX was administered as 1-h intravenous infusion every two weeks for at least four courses. The starting dose was 40 mg/m(2) (level 1) and the dose was escalated to 50 mg/m(2) (level 2) and 60 mg/m(2) (level 3) in consequent patient cohorts. Nine patients were examined in this study. The treatments were completely performed in all cohorts. Mean treatment delay ranged from 0 to 2.0 days. Dose level did not affect treatment delay. At the first dose level, no patients experienced grade 3/4 neutropenia. Two patients in level 2 experienced grade 3/4 neutropenia. In level 3, all patients had grade 4 neutropenia. Nonhematologic toxicities were tolerable. Of eight patients with measurable disease, all patients in level 1 showed progressive disease, and all patients in level 2 were no-change. There were two responders showing complete response and partial response and one case was no-change in level 3. The present study showed that biweekly administration of 60 mg/m(2) DTX was feasible for recurrent ovarian cancer.


Fetal growth restriction in preterm infants and cardiovascular function at five years of age.
We have previously reported an increased cardiac workload in newborn preterm small (SGA) infants, but not in infants appropriate for gestational age (AGA). We hypothesized that these cardiovascular changes will persist at follow-up at 5 years of age. We assessed blood pressure, echocardiography, and skin perfusion with laser Doppler flowmetry in 22 SGA (821 +/- 248 g, 28.5 +/- 2.5 gestational weeks) and in 25 AGA (1065 +/- 241 g, 27.6 +/- 0.8 weeks) preterm children at age 5 years. Laser Doppler flowmetry also was used in 13 control children (3982 +/- 425 g, 40.4 +/- 1.8 weeks). The preterm children in both the SGA and AGA groups had similar higher systolic blood pressures, increased interventricular septum thicknesses, and smaller left ventricular end-diastolic diameters compared with population reference values. Maximal endothelium-independent perfusion to sodium nitroprusside was higher and maximal endothelium-dependent perfusion to acetylcholine reached a plateau earlier in the AGA preterm group than in the control group. Prematurity may impair cardiovascular function independently of intrauterine growth restriction. Altered cardiac dimensions and differences in perfusion responses may reflect increased cardiac afterload.


[Influence of diurnal variation in the size of acute myocardial infarction].
To evaluate whether the size of acute myocardial infarction (AMI) shows circadian variability. An observational, prospective study. A 12-bed coronary care unit. Consecutive patients diagnosed with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. The patients were divided into two groups according to the time of onset of AMI symptoms (Group A: 0-12hours, Group B: 12-24hours). Age, sex, cardiovascular risk factors, coronary anatomy, left ventricular ejection fraction, infarct location, time from onset of symptoms to reperfusion, presence of heart failure upon admission, and peak troponin I value. A total of 108 patients with a diagnosis of STEMI were included. Patients in group A showed a higher troponin I concentration compared to group B (troponin I: 70.85±16.38 versus 60.90±22.92ng / ml, p=0.003). In the multivariate analysis the onset of AMI between 0-12hours was identified as an independent predictor of infarct size (OR: 1.133, 95%CI 1.012-1.267, p=0.01). An onset of AMI between 0-12hours results in a significantly larger final size of necrosis compared with any other time of presentation.


Climate effects on land management and stream nitrogen concentrations in small agricultural catchments in Norway.
Land use and climate change can impact water quality in agricultural catchments. The objectives were to assess long-term monitoring data to quantify changes to the thermal growing season length, investigate farmer adaptations to this and examine these and other factors in relation to total nitrogen and nitrate water concentrations. Data (1991-2017) from seven small Norwegian agricultural catchments were analysed using Mann-Kendall Trend Tests, Pearson correlation and a linear mixed model. The growing season length increased significantly in four of seven catchments. In catchments with cereal production, the increased growing season length corresponded to a reduction in nitrogen concentrations, but there was no such relationship in grassland catchments. In one cereal catchment, a significant correlation was found between the start of sowing and start of the thermal growing season. Understanding the role of the growing season and other factors can provide additional insight into processes and land use choices taking place in agricultural catchments.


Crystalline structure analysis of cellulose treated with sodium hydroxide and carbon dioxide by means of X-ray diffraction and FTIR spectroscopy.
Crystalline structures of cellulose (named as Cell 1), NaOH-treated cellulose (Cell 2), and subsequent CO2-treated cellulose (Cell 2-C) were analyzed by wide-angle X-ray diffraction and FTIR spectroscopy. Transformation from cellulose I to cellulose II was observed by X-ray diffraction for Cell 2 treated with 15-20 wt% NaOH. Subsequent treatment with CO2 also transformed the Cell 2-C treated with 5-10 wt% NaOH. Many of the FTIR bands including 2901, 1431, 1282, 1236, 1202, 1165, 1032, and 897 cm(-1) were shifted to higher wave number (by 2-13 cm(-1)). However, the bands at 3352, 1373, and 983 cm(-1) were shifted to lower wave number (by 3-95 cm(-1)). In contrast to the bands at 1337, 1114, and 1058 cm(-1), the absorbances measured at 1263, 993, 897, and 668 cm(-1) were increased. The FTIR spectra of hydrogen-bonded OH stretching vibrations at around 3352 cm(-1) were resolved into three bands for cellulose I and four bands for cellulose II, assuming that all the vibration modes follow Gaussian distribution. The bands of 1 (3518 cm(-1)), 2 (3349 cm(-1)), and 3 (3195 cm(-1)) were related to the sum of valence vibration of an H-bonded OH group and an intramolecular hydrogen bond of 2-OH ...O-6, intramolecular hydrogen bond of 3-OH...O-5 and the intermolecular hydrogen bond of 6-O...HO-3', respectively. Compared with the bands of cellulose I, a new band of 4 (3115 cm(-1)) related to intermolecular hydrogen bond of 2-OH...O-2' and/or intermolecular hydrogen bond of 6-OH...O-2' in cellulose II appeared. The crystallinity index (CI) was obtained by X-ray diffraction [CI(XD)] and FTIR spectroscopy [CI(IR)]. Including absorbance ratios such as A1431,1419/A897,894 and A1263/A1202,1200, the CI(IR) was evaluated by the absorbance ratios using all the characteristic absorbances of cellulose. The CI(XD) was calculated by the method of Jayme and Knolle. In addition, X-ray diffraction curves, with and without amorphous halo correction, were resolved into portions of cellulose I and cellulose II lattice. From the ratio of the peak area, that is, peak area of cellulose I (or cellulose II)/total peak area, CI(XD) were divided into CI(XD-CI) for cellulose I and CI(XD-CII) for cellulose II. The correlation between CI(XD-CI) (or CI(XD-CII)) and CI(IR) was evaluated, and the bands at 2901 (2802), 1373 (1376), 897 (894), 1263, 668 cm(-1) were good for the internal standard (or denominator) of CI(IR), which increased the correlation coefficient. Both fraction of the absorbances showing peak shift were assigned as the alternate components of CI(IR). The crystallite size was decreased to constant value for Cell 2 treated at >or= 15 wt% NaOH. The crystallite size of Cell 2-C (cellulose II) was smaller than that of Cell 2 (cellulose I) treated at 5-10 wt% NaOH. But the crystallite size of Cell 2-C (cellulose II) was larger than that of Cell 2 (cellulose II) treated at 15-20 wt% NaOH.


ANT-DBS in epilepsy shows no effect on selected neuropsychiatric tests.
Deep brain stimulation of the anterior thalamic nucleus (ANT-DBS) is an established option in treatment-resistant epilepsy and obtained FDA approval in 2018. Increased psychiatric comorbidity is well known in epilepsy. The main objective of this study was to investigate possible neuropsychiatric treatment-related changes in patients receiving ANT-DBS. Bilateral ANT electrodes were implanted in 18 adult patients with refractory epilepsy in a randomized, double-blinded study. Immediately after implantation, patients were randomized to stimulation ON (n = 8) or OFF (n = 10) for the first 6 months (blinded phase). During the next six months (open phase), both groups received active stimulation. Neuropsychiatric assessment was conducted before implantation (T1), at the end of the blinded period (T2), and 1 year after implantation (T3). Comparing preoperative status (T1) and 12 months (T3), postoperative outcome in all patients did not show significant differences between the two groups for any of the applied tests. Groupwise comparisons across the two first time points (the blinded period, representing the randomized controlled trial) showed no significant differences between the two groups in any of the neuropsychiatric parameters studied. Comparing test results after 6 months of stimulation in both groups (sum of ON group T1 to T2 and OFF group T2 to T3) did not show significant changes for any of the psychiatric assessments. Our results indicate that ANT-DBS has limited effect concerning psychiatric issues. Subjective side effects were, however, reported in individual patients.


Protein consumptions in stroke patients.
Stroke is one of the most common causes of disabilities and death all over the world. The mortality rate of stroke is predicted to be doubled by 2030 in the Middle East countries. Nutrition is an effective strategy in prevention and management of stroke. This study assessed the relationship between various protein types and stroke risk. This hospital-based case-control study was performed in a University hospital. The data regarding consumption of usual food intake of 69 cases (46 men and 23 women) and 60 controls (30 men and 30 women) was collected with a food frequency questionnaire (FFQ). The mean consumption of red and white meat and vegetable and processed proteins consumption were compared between two groups. The percent of total of daily protein intake were lower in patients with stroke in both sexes (25.92% vs 30.55% in men and 30.7% vs 31.14% in women). Lower protein consumption may be observed in patients with stroke patients in both sex.


Differential regulation of fos and jun gene expression and AP-1 cis-element activity by endothelin isopeptides. Possible implications for mitogenic signaling by endothelin.
Endothelins (ET) are potent vasoconstrictor peptides that also function as mitogens for numerous cell types. Although regulation of second messenger pathways by ET peptides has been extensively investigated, little is known about the pathways of nuclear signaling by which ET controls gene expression. The present experiments investigated whether fos and jun contribute to nuclear signaling and gene regulation by ET isopeptides. ET isopeptides induced a subset of fos and jun mRNAs in mesangial cells, including c-fos, fra-1, c-jun, and JunB. fos and jun mRNAs were induced as members of the immediate-early gene response. Activation of the high affinity ET receptor moderately increased c-fos and fra-1 mRNA, whereas activation of the low affinity receptor markedly induced both fos and jun mRNAs. Thus, different ET receptor subtypes evoke distinct patterns of fos and jun induction. Prominent isopeptide- and cell-specific differences in the magnitude and kinetics of fos and jun expression were observed. Most striking was the marked elevation of c-fos steady-state mRNA and protein by ET-1, as compared with ET-3. In addition, ET-1, but not ET-3, increased transcriptional activity conferred by an AP-1 cis-element and directed collagenase gene expression. These results suggest that differential regulation of fos and jun expression and of AP-1 cis-element activity by ET isopeptides contributes to regulation of gene expression by ET. Furthermore, a role for AP-1 in mitogenic signaling by ET is suggested by the close correlation between AP-1 cis-element activity and cell growth.


Frequency and clinical characteristics of early gastric cancer in comparison to advanced gastric cancer in a health area of Spain.
Gastric cancer (GC) incidence is currently decreasing; however, survival is still low. Early GC (EGC) has better prognosis and it could be cured by endoscopic methods. Observational study of a retrospective cohort of all patients with GC during a five-year period in a health area of Spain. EGC diagnosis was defined as mucosal or submucosal (T1) cancers regardless of lymph node involvement, whereas the advanced GC were T2-T4. 209 patients were included, and 26 (12%) of them were EGC. There was no difference between EGC and advanced GC in age, sex, HP infection, precancerous lesions or histological type. Other characteristics of EGC were different from advanced GC: location (antrum and incisura in 76% vs 38%, p=0.01), alarm symptoms (69% vs 90%, p<0.01), curative treatment (100% vs 30%, p<0.01), performance status (PS 0-1: 92% vs 75%, p=0.03) and survival (85% vs 20%, p<0.001). Among patients who received curative treatment, 98% (79/81) underwent surgery and 2% (2/81) were treated by mucosectomy. Seven (27%) patients with EGC could have benefited from treatment by endoscopic submucosal resection. EGC frequency was low (12% of GCs) in our health area. EGC had a high percentage of alarm symptoms, and was located in the distal third of the stomach (antrum and incisura) and had better prognosis compared to advanced GC. Strategies to increase detection and endoscopic treatment of EGC should be implemented.


Responses of the trunk routes of a harvester ant to plant density.
Messor barbarus is a Mediterranean harvester ant that constructs physically defined trunk routes on the ground to connect nest entrances with foraging areas. Some responses of these trunk routes to plant density (and therefore resource abundance) were analyzed by testing the preferential allocation of different parts (trunk route ends, segments and branching points) in a patchy environment. Maps of grass density in four categories and Messor barbarus trunk routes were compiled for a Mediterranean pasture in Central Spain over four consecutive years. The proportions of the density categories in each year were used to calculate random expected frequencies of the trunk route points and the predominance of higher or lower grass densities. Trunk route ends discriminate and selectively reach patches with a greater abundance of resources in all study years. Branching points are also allocated preferentially in areas with higher vegetation density, but only in years with a predominance of the higher categories of grass density. In these years, the colonies of Messor barbarus have a "phalanx" strategy at a colonial level, and branching is more profuse. Finally, trunk route segments do not indicate any preference for crossing determined vegetation densities, but rather connect successive branching points or trunk route ends by the shortest route. These results concur with a model of structural strategy change ("guerilla" - "phalanx") (Hutchings 1988) at the level of trunk routes. They are probably constituted by "transitory" sections with few branches, that expand other more profusely branched sections which are more dedicated to foraging.


Radiation Injuries.
Radiation-related injuries are rare. Yet the consequences of an event involving a radiation source can be substantial. As with any clinical emergency that rarely occurs, we are typically less prepared to deal with the situation. Compounding the crisis will be the "worried well" population who may believe that they too are contaminated or suffering from radiation poisoning and report to the hospital for evaluation. Identifying and triaging those who are sick or injured, managing the surge of patients, and knowing where resources can be accessed are all essential.


Molecular study of Porcine Circovirus type 2 in wild boars and domestic pigs in Uruguay from 2010 to 2014: Predominance of recombinant circulating strains.
Porcine Circovirus type 2 (PCV2) is a worldwide distributed pathogen and one of the most economically relevant swine infections. Four genotypes have been recognized and it is well known that PCV2a, PCV2b and PCV2d have a global distribution. However, the information about recombinant strains circulation and their influence in driving PCV2 evolution is a poorly studied area. In Uruguay, PCV2 associated symptoms began to be frequently observed in pigs from different farms since 2010. The main purpose of this study was to thoroughly investigate the molecular epidemiology of PCV2 in nationwide swine herds and free-living wild boars during the period 2010-2014, providing an extensive viral sequence dataset. Surprisingly, the findings revealed a predominance of recombinant strains circulation, evidencing for the first time in the field that PCV2 recombination can lead to the emergence of strains able to compete and potentially displace parental ones. In addition, the circulation of the genotypes PCV2d (29%), PCV2b (10.5%) and PCV2a (7.9%) were also observed. Since 2013, a high circulation of PCV2d was identified in the country and probably reflected the recent global scenario of the emergence of this genotype. In addition, fluctuations in the frequency of PCV2 infection in the period evaluated may suggest a limitation of biosecurity strategies implemented in Uruguay for the disease control, including the instability of vaccination practices. On the other hand, the sustained PCV2 infection observed in wild boar population and the similarity among circulating viral strains from these animals and domestic pigs, suggested that wild animals could serve as permanent reservoir of the disease. Altogether, this work put forward that many factors play a role in PCV2 heterogeneity including rapid viral spread and evolution, recombination, wide movement within national boundaries and multiples introduction events resulting of international trade. Continuous monitoring of viral epidemiology is needed to better understand the PCV2 population dynamics in Uruguay and the development of appropriate strategies are required for disease control.


Limited nucleosome migration can completely randomize DNA repair patches in intact human cells.
Following irradiation of human cells with ultraviolet light, DNA repair patches are initially inserted near the 5' and 3' ends of nucleosome core DNA leaving a "gap" in repair synthesis (of approximately 50 bases) near the center of the core DNA. With time, however, these same repair patches become randomized, apparently by nucleosome migration. We have developed both an analytical expression and a computer algorithm (which simulates nucleosome migration along DNA) to determine the average distance nucleosomes must migrate to change the initial, non-uniform distribution of repair patches in nucleosomes to a random distribution. Both of these methods yielded the same result: nucleosomes must migrate an average of about 50 base-pairs in either direction to produce the randomization observed.


Commensal bacteria influence Escherichia coli O157:H7 persistence and Shiga toxin production in the mouse intestine.
The presence of commensal flora reduced colonization of Escherichia coli O157:H7 and production of Shiga toxin (Stx) in the murine intestine. Stx production was not detected in mice colonized with E. coli that were resistant to the Shiga toxin phage, but it was detected in mice colonized with phage-susceptible E. coli.


The influence of gastric motility on the intraluminal behavior of fosamprenavir.
In fasting conditions, the gastrointestinal system contracts according to the interdigestive migrating motor complex (MMC), in which phases of quiescence (MMC phase I) alternate with phases of medium (MMC phase II) to very strong (MMC phase III) contractions. The time of drug intake relative to this cyclic motility pattern may cause variations in formulation behavior. To explore this hypothesis, a cross-over study was performed in healthy volunteers with an immediate release tablet of fosamprenavir (Telzir) which was administered in either MMC phase I or MMC phase II, as determined by high-resolution manometry. In the intestinal tract, fosamprenavir is rapidly hydrolyzed to the active compound amprenavir by alkaline phosphatases. Drug concentrations of both prodrug and drug were determined in the stomach and duodenum and linked to simultaneously assessed systemic concentrations. In 5 out of 6 healthy volunteers, the gastric release of fosamprenavir and the systemic uptake of amprenavir were affected by the MMC phase in which the tablet was administered. The intragastric disintegration of the tablet was faster and less variable after administration in MMC phase II, resulting in faster and less variable uptake of amprenavir in the systemic circulation. Mean plasma tmax values were 157 (±72.0) and 73.3 (±27.3) min after administration in MMC phase I and MMC phase II, respectively. The study clearly identified the time of oral drug intake relative to the interdigestive motility pattern as a possible source of variation in gastrointestinal drug behavior and absorption.


Flow cytometry analysis of platelet cyclooxygenase-2 expression: induction of platelet cyclooxygenase-2 in patients undergoing coronary artery bypass grafting.
There are conflicting reports about the expression of cyclooxygenase (COX)-2 in human platelets. The present study describes a flow cytometric method for the measurement of platelet COX. Both COX-1 and COX-2 were shown to be expressed in platelets from patients undergoing a coronary artery bypass graft. There was a significant increase in COX-2 expression at day 5 as compared with pre-surgery values (mean fluorescence 12.31 +/- 0.88 versus 9.15 +/- 0.88; means +/- SEM, n = 7, P < 0.05), whereas COX-1 levels did not change (13.45 +/- 1.11 versus 12.38 +/- 1.41; n = 7, P > 0.05).


Comparison of the Effect of Dexamethasone and Tranexamic Acid, Separately or in Combination on Post-Rhinoplasty Edema and Ecchymosis.
Dexamethasone and tranexamic acid are used to decrease post-rhinoplasty periorbital edema and ecchymosis. We compared the impact of each medication separately or in combination in this regard. A prospective, randomized triple-blinded study was undertaken on 60 patients who underwent primary open rhinoplasty. They were divided into four groups: Group D (n = 15) received 8 mg dexamethasone, group T (n = 15) received 10 mg/kg tranexamic acid, group DT (n = 15) received both 8 mg dexamethasone and 10 mg/kg tranexamic acid, and group P (n = 15) received neither medication and served as the placebo control group. The medications were given intravenously (IV) 1 h before and three doses every 8 h postoperatively. Digital photographs were taken on the first, third and seventh postoperative days. One expert examiner blinded to the study evaluated the periorbital edema and ecchymosis on a scale of 0-4. Periorbital edema and ecchymosis were examined in all groups. In group D, group T and group DT, periorbital edema and ecchymosis ratings were significantly lower compared with the control group (p < 0.01). No statistically significant difference was seen in preventing or decreasing both periorbital edema and ecchymosis among group D, group T and group DT. Tranexamic acid and dexamethasone, separately or in combination, had similar effects in reducing periorbital edema and ecchymosis in open rhinoplasty. Combined application did not show a significantly higher beneficial effect in this regard. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Changes in cytokine production in vitro during the early phase of birch-pollen immunotherapy.
The kinetics of the immunological mechanisms during allergen-specific immunotherapy (IT) has not been thoroughly evaluated. In this investigation we study the changes in T-cell responses during the early phase of IT. Ten patients (IT group) with birch-pollen allergy were treated with conventional IT. Blood samples were collected at regular intervals for specific immunoglobulin (Ig)E measurements and preparation of peripheral blood mononuclear cells (PBMC). Seven allergic control patients (AC group) were included during the subsequent birch-pollen season. The PBMC were stimulated with birch-pollen extract or tetanus toxoid (TT) and mitogens. After a short decrease, probably owing to seasonal variation, the birch-pollen-specific proliferation and the interleukin (IL)-4, IL-5, and IL-10 production significantly increased when reaching the maintenance dose and during the subsequent pollen season. The increase in IL-4 correlated with a temporary increased serum level of birch-pollen-specific IgE. Interestingly, also the TT-specific response was affected by IT, resulting in weaker, but in time similar, changes in proliferation and cytokine production as in the birch-pollen-specific response. We speculate that the early phase of IT might lead to systemic changes in the capacity of Th2-like cytokine production, and that the early increase in allergen-specific IgE is a consequence of enhanced IL-4 production.


Autobiographical memory loss in Alzheimer's disease: The role of the reminiscence bump.
Research on autobiographical memory loss in Alzheimer's disease (AD) is characterized by conflicting findings concerning a possible sparing of older memories. The literature shows evidence for both a negative temporal gradient, a flat gradient and a reminiscence bump - that is, a disproportionally high frequency of memories from early adulthood relative to surrounding periods. Here, we expanded the number of lifetime periods of the Autobiographical Memory Interview (AMI; Kopelman, Wilson & Baddeley, 1989, 1990) from the standard three to seven in order to increase the sensitivity of the test to variations in the temporal distribution of autobiographical memories across the life span. Twenty-five older adults diagnosed with AD (MMMSE = 21.16, SD = 5.08) and a matched sample of 30 healthy, older adults were assessed. The temporal distribution for personal semantic information in AD showed a temporal gradient steadily decreasing from middle childhood to present life, consistent with predictions derived from consolidation theories. In comparison, the temporal distribution of incidents/episodic memories produced by AD patients in response to the expanded AMI showed a predominance of autobiographical memories from age 6 to 30, followed by a steep drop in memory referring to events that had occurred after age 30. This distribution challenges standard theories of retrograde amnesia in AD by showing neither a temporal gradient, decreasing progressively from early to later life, nor a flat gradient. In contrast, the distribution is consistent with the reminiscence bump identified in autobiographical memory research. Schematization and retrieval support provided by cultural life scripts are discussed.


Effect of nimesulide on the serum levels of hyaluronan and stromelysin-1 in patients with osteoarthritis: a pilot study.
This prospective preliminary single-blind study was conducted in patients suffering from osteoarthritis (OA) and requiring non-steroidal anti-inflammatory drugs (NSAIDs) to determine to what extent nimesulide (200 mg/day) and ibuprofen (1200 mg/day) could induce significant changes in the serum levels of matrix metalloproteinase-3 (MMP-3), tissue inhibitor-1 of MMPs (TIMP-1), hyaluronan (HA) and YKL-40 after a therapeutic time period of 28 days. The four biochemical parameters were assessed by using immunoassays. Nimesulide significantly reduced the serum levels of both HA and MMP-3, whereas ibuprofen increased moderately but significantly the serum concentrations of MMP-3 and had no effect on the serum concentrations of HA. The two NSAIDs were unable to change the serum levels of both TIMP-1 and YKL-40. These results suggest that nimesulide might have a favourable effect on the metabolism of OA joints.


A facile synthesis of new 2-carboxamido-3-carboxythiophene and 4,5,6,7-tetrahydro-2-carboxamido-3-carboxythieno[2,3-c]pyridine derivatives as potential endothelin receptors ligands.
Endothelins (ETs) are the most ubiquitous, highly potent and unusually long-lasting peptidic constrictors of human vessels known. Elevated levels of the plasma concentration of ETs were observed in several diseases such as hypertension, acute myocardial infarction, congestive heart failure, renal failure, pulmonary hypertension, and atherosclerosis. ETs exert their activities via specific seven-transmembrane, G protein-coupled receptors. To date two receptor subtypes, endothelin A (ET(A)) and endothelin B (ET(B)), have been identified and cloned. A literature survey revealed that a number of compounds that bind ET receptors with affinity and selectivity are known, nevertheless these compounds belong only to few chemical classes. The aim of this work is the identification of an "hit compound" with novel chemical structure endowed with reasonable ET affinity and selectivity. Accordingly, new variously substituted 2-carboxamido-3-carboxythiophene derivatives (29-52) were synthesized. These compounds were tested for their ability to inhibit ETs binding in radioligand binding assay using CHO cells stably expressing human ET(A) and ET(B) receptors.


Never smile at a crocodile: Gaping behaviour in the Nile crocodile at Ndumo Game Reserve, South Africa.
Gaping is a regularly observed behaviour in crocodilians globally but is still poorly understood in relation to external variables which could trigger this behaviour. The occurrence of gaping behaviour was investigated in a large wild population of Nile crocodiles (Crocodylus niloticus) during the dry and wet seasons at Nyamithi Pan, Ndumo Game Reserve, South Africa. This is one of the longest crocodile gaping behaviour studies conducted in the wild, with 300 h of observations conducted over two seasons resulting in 1120 gaping behaviours recorded. The most common size class observed was between 1.5 and 2.5 m (n = 697), which accounted for 62.2% of the gaping observations. A significant decrease in gaping duration was observed as ambient temperatures increased, and the gape duration was longer at a higher degree angle. In addition, an increase in gape duration was observed as the number of neighbouring crocodiles increased. These results suggest gaping behaviour occurs when there are other crocodiles nearby and when temperatures do not necessitate thermoregulation. The study suggests that gaping could be used as a form of thermoregulation and intra-species communication.


Antimicrobial activities of metabolites isolated from endophytic Aspergillus flavus of Sarcophyton ehrenbergi supported by in-silico study and NMR spectroscopy.
Endophytic Aspergillus species produce countless valuable bioactive secondary metabolites. In the current study, Aspergillus flavus an endophyte from the soft coral Sarcophyton ehrenbergi was chemically explored and the extracted phytoconstituents were subsequently evaluated for antimicrobial activity. This is accomplished by employing nuclear magnetic resonance (NMR) spectroscopy and computational techniques. Additionally, An in vitro anticancer analysis of A. flavus total extract against breast cancer cells (MCF-7) was investigated. Six compounds were separated from the crude alcohol extract of the endophytic Aspergillus flavus out of which anhydro-mevalonolactone was reported for the first time. The anti-fungal and anti-Helicobacter pylori properties of two distinct compounds (Scopularides A and B) were assessed. Additionally, computational research was done to identify the binding mechanisms for all compounds. Both the compounds were found to be active against H. pylori with minimum inhibitory concentration (MIC) values ranging from 7.81 to 15.63 µg/ mL as compared with clarithromycin 1.95 µg/ mL. Scopularides A was potent against both Candida albicans and Aspergillus niger with MIC values ranging from 3.9 to 31.25 µg/ mL, while scopularides B only inhibits Candida albicans with MIC value of 15.63 µg/ mL and weak inhibitory activity against A. niger (MIC = 125 µg/ mL). Furthermore, cytotoxic activity showed a significant effect (IC50: 30.46 mg/mL) against MCF-7 cells. Our findings report that cytotoxic activity and molecular docking support the antimicrobial activity of Aspergillus flavus, which could be a promising alternative source as a potential antimicrobial agent.


Characterization of bovine pancreatic ductal cells isolated by a perfusion-digestion technique.
Bovine pancreatic ductal cells isolated by perfusing an enzyme solution into the lumen of the main duct were obtained as sheets of cells. Morphologic features of these cells were those of pancreatic ductal epithelial cells. These cells also contained alcian blue/periodic acid-Schiff positive material and bound lectins, and they stained for keratin in the same manner as intact ductal epithelium. In culture, the plating efficiency was high (13.6%) as determined by DNA content before and after 24 h plating, perhaps due to the gentle isolation technique and the isolation of sheets of cells rather than a single cell. Cell doubling time was 34.4 h in Eagle's minimal essential medium with 10% heat inactivated fetal bovine serum and antibodies, and over 95% of the cells incorporated [3H]thymidine during a 6 h labeling period after 4 d in primary culture. Isolated cells grew best in medium CMRL 1066 with 10% heat inactivated fetal bovine serum as determined by measuring DNA content.


The pre-addition of "blocking" proteins decreases subsequent cellulase adsorption to lignin and enhances cellulose hydrolysis.
The pre-adsorption of non-catalytic/blocking proteins onto the lignin component of pretreated biomass has been shown to significantly increase the effectiveness of subsequent enzyme-mediated hydrolysis of the cellulose by limiting non-productive enzyme adsorption. Layer-by-layer adsorption of non-catalytic proteins and enzymes onto lignin was monitored using Quartz Crystal Micro balancing combined with Dissipation monitoring (QCM-D) and conventional protein adsorption. These methods were used to assess the interaction between soft/hardwood lignins, cellulases and the three non-catalytic proteins BSA, lysozyme and ovalbumin. The QCM-D analysis showed higher adsorption rates for all of the non-catalytic proteins onto the lignin films as compared to cellulases. This suggested that the "blocking" proteins would preferentially adsorb to the lignin rather than the enzymes. Pre-incubation of the lignin films with blocking proteins resulted in reduced adsorption of cellulases onto the lignin, significantly enhancing cellulose hydrolysis.


Efficacy and safety of Ayurvedic herbs in diarrhoea-predominant irritable bowel syndrome: A randomised controlled crossover trial.
Herbal medicines have been used widely for the treatment of irritable bowel syndrome (IBS) patients. The aim of this study is to investigate efficacy and safety of an Ayurvedic herbal compound preparation made from: Murraya koenigii (curry), Punica granatum (pomegranate) and Curcuma longa (turmeric), compared to a placebo in patients with diarrhoea predominant IBS. This trial was conducted as a randomised placebo-controlled crossover trial with randomised sequence of verum and placebo for each patient. Verum and placebo were provided as ground powders and delivered in sealed containers. Patients and outcome assessors were blinded. Patients were advised to ingest the decoction twice daily for 4 weeks. The primary outcome measure was IBS symptom intensity; secondary outcomes included: quality of life, anxiety and depression, compliance and safety. 32 IBS patients were included in the trial (19 females, mean age 50.3±11.9years). Eleven people dropped out during the trial resulting in 37 complete verum and 35 complete placebo phases. No group differences were found between verum and placebo for IBS symptom intensity (difference 24.10; 95% CI: -17.12; 65.32, p=0.26). The same was true for secondary outcomes. Compliance was satisfactory to good and the preparation appeared to be safe, but one third of the patients registered at least one minor adverse event that might be related to the study interventions. An Ayurvedic herbal preparation made from Murraya koenigii, Punica granatum and Curcuma longa appeared to be no more effective in improving diarrhoea predominant irritable bowel symptoms than placebo.


Persistent sciatic artery: bilateral percutaneous transluminal angioplasty in ischemic disease.
Persistent sciatic artery (PSA) is a rare vascular anomaly that results from failure of an embryonal artery to the lower extremities to regress during fetal development. Aneurysm formation, thromboembolism, and arterial occlusions may complicate this abnormality. We report a patient with complete bilateral PSA and intermittent claudication who was treated by bilateral percutaneous angioplasty.


Betaine and choline status modify the effects of folic acid and creatine supplementation on arsenic methylation in a randomized controlled trial of Bangladeshi adults.
Methylation of ingested inorganic arsenic (InAs) to monomethyl- (MMAs) and dimethyl-arsenical species (DMAs) facilitates urinary arsenic elimination. Folate and creatine supplementation influenced arsenic methylation in a randomized controlled trial. Here, we examine if baseline status of one-carbon metabolism nutrients (folate, choline, betaine, and vitamin B12) modified the effects of FA and creatine supplementation on changes in homocysteine, guanidinoacetate (GAA), total blood arsenic, and urinary arsenic metabolite proportions and indices. Study participants (N = 622) received 400 or 800 μg FA, 3 g creatine, 400 μg FA + 3 g creatine, or placebo daily for 12 weeks. Relative to placebo, FA supplementation was associated with greater mean increases in %DMAs among participants with betaine concentrations below the median than those with levels above the median (FDR < 0.05). 400 μg FA/day was associated with a greater decrease in homocysteine among participants with plasma folate concentrations below, compared with those above, the median (FDR < 0.03). Creatine treatment was associated with a significant decrease in %MMAs among participants with choline concentrations below the median (P = 0.04), but not among participants above the median (P = 0.94); this effect did not significantly differ between strata (P = 0.10). Effects of FA and creatine supplementation on arsenic methylation capacity were greater among individuals with low betaine and choline status, respectively. The efficacy of FA and creatine interventions to facilitate arsenic methylation may be modified by choline and betaine nutritional status. Clinical Trial Registry Identifier: NCT01050556, U.S. National Library of Medicine, https://clinicaltrials.gov ; registered January 15, 2010.


Adjunctive Systemic Corticosteroids for Hospitalized Community-Acquired Pneumonia: Systematic Review and Meta-Analysis 2015 Update.
Previous randomized controlled trials (RCTs) and meta-analyses evaluated the efficacy and safety of adjunctive corticosteroids for community-acquired pneumonia (CAP). However, the results from them had large discrepancies. The eligibility criteria for the current meta-analysis were original RCTs written in English as a full article that evaluated adjunctive systemic corticosteroids adding on antibiotic therapy targeting typical and/or atypical pathogen for treating hospitalized human CAP cases. Four investigators independently searched for eligible articles through PubMed, Embase, and Cochrane databases. Random model was used. The heterogeneity among original studies and subgroups was evaluated with the I(2) statistics. Of 54 articles that met the preliminary criteria, we found 10 eligible RCTs comprising 1780 cases. Our analyses revealed following pooled values by corticosteroids. OR for all-cause death: 0.80 (95% confidence interval (95% CI) 0.53-1.21) from all studies; 0.41 (95% CI 0.19-0.90) from severe-case subgroup; 0.21 (95% CI 0.0-0.74) from intensive care unit (ICU) subgroup. Length of ICU stay: -1.30 days (95% CI (-3.04)-0.44). Length of hospital stay: -0.98 days (95% CI (-1.26)-(-0.71)). Length to clinical stability: -1.16 days (95% CI (-1.73)-(-0.58)). Serious complications do not seem to largely increase by steroids. In conclusion, adjunctive systemic corticosteroids for hospitalized patients with CAP seems preferred strategies.


Parotid gland tumours in Turkish population: analysis of 165 patients.
Retrospective data on 165 patients who presented with a parotid mass and underwent surgery in our clinics during 2000-2009 were examined. The obtained data (demographic data, surgical procedures, histopathological diagnoses) were compared to similar studies to make contributions to the literature. Patients were classified according to their histopathological diagnosis. Surgical procedures and patient follow-up were clarified. The results are presented as means and standard deviations. Of the 165 masses, 134 (81.3%) were benign and 31 (18.7%) were malignant. Pleomorphic adenoma was the most common benign tumour (79 patients, 59%). Lymphoma and adenoid cystic carcinoma were equally common and were the most common malignant parotid gland tumours (both 6 patients, 19.3%). The most frequent surgical procedure was superficial parotidectomy (92 patients, 55.7%), and the most commonly encountered surgical complication was facial paralysis (12 patients, 7.2%). Our data are generally in line with the literature but lymphoma was more common than in most previous reports. Although the number of cases was low, the high incidence of parotid gland lymphoma was remarkable.


1,1'-Methyl-enebis{4-[(E)-2-(pyridin-4-yl)ethen-yl]pyridinium} dibromide dihydrate.
The chevron-shaped cations of the title hydrated salt, C25H22N4 2+·2Br-·2H2O, are arranged in back-to-back alternating directions to form a zigzag ribbon propagating along the [010] direction. Inter-molecular inter-actions comprising these ribbons are π-π inter-actions between the pyridinium and adjacent pyridyl rings, as well as O-H⋯O hydrogen bonding between water molecules and two adjacent pyridyl N atoms. Half of the cation is generated by the mirror plane. The water O atoms, the central C atom and one Br atom are located on this mirror plane while the other Br atom is on a twofold screw axis.


Effect of coppice conversion into high forest on soil organic C and nutrients stock in a Turkey oak (Quercus cerris L.) forest in Italy.
In forest ecosystems, a variety of abiotic and biotic soil forming factors drives soil organic matter (SOM) and nutrients cycling with a profitable outcome on climate change mitigation. As a consequence, type and intensity of forest management, through its impact on carbon (C) and nutrient soil stocks, can be considered as an additional soil forming force. In this study, we investigated the influence of the coppice conversion into high forest on pedogenesis and on soil C and nutrient (N, P, Ca, Mg, and K) stocks, fifty years later the beginning of the conversion-cycle. The trial was established in a Turkey oak forest historically managed under the coppice system in central Italy. Specifically, we considered tree population density (natural evolution - control, moderate thinning, heavy thinning) where soil samples were collected according to genetic horizon to estimate C, N, and P stocks both in the forest floor and at fixed depth intervals (0-30, 30-50 and 50-75 cm). Further, the stocks of exchangeable Ca, Mg, and K were also assessed for the mineral layers. The results showed that litter and the upper layer of mineral soil (0-30 cm) contained a similar quantity of C (about 74-83 Mg ha-1), independently of the trials and no differences were observed also in the whole soil stocks (about 192-213 Mg ha-1). The comparison of the mean stocks calculated per 1-cm of thickness of organic (O), organo-mineral (OM), and mineral (M) layers, although it did not display any difference among trials (excepted for P and Mg), showed a similar capability of the organo-mineral horizons to store C and nutrients compared with the organic ones (e.g., about 6-12 Mg ha-1, 0.3-0.5 Mg ha-1 and 0.5-1.5 kg ha-1 for C, N and P, respectively). Our findings showed that thinning operated on Turkey oak coppice did not affect soil capacity to store C and nutrients. These results suggested that the forest ecosystem itself is the main soil forming force and this is consistent with the target of adopting forest management able to control the global C cycle through the storage of SOM in the mineral soil rather than in forest floor, where SOM turnover is faster.


Glandular mast cells with distinct phenotype are highly elevated in chronic rhinosinusitis with nasal polyps.
Although chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is characterized by T(H)2 inflammation, the role of mast cells is poorly understood. The objective of this study was to investigate the presence, localization, and phenotype of mast cells in patients with CRS. We collected nasal tissue and nasal lavage fluid from patients with CRS and control subjects. We analyzed mRNA for the mast cell proteases tryptase, chymase, and carboxypeptidase A3 by using real-time PCR and measured mast cell protease proteins by using ELISA, immunohistochemistry, and immunofluorescence. Tryptase mRNA was significantly increased in nasal polyps (NPs) from patients with CRSwNP (P< .001) compared with uncinate tissue from patients with CRS or control subjects. Tryptase protein was also elevated in NPs and in nasal lavage fluids from patients with CRSwNP. Immnohistochemistry showed increased numbers of mast cells in epithelium and glands but not within the lamina propria in NPs. The mast cells detected in the epithelium in NPs were characterized by the expression of tryptase and carboxypeptidase A3 but not chymase. Mast cells expressing all the 3 proteases were abundant within the glandular epithelium of NPs but were not found in normal glandular structures. Herein we demonstrated a unique localization of mast cells within the glandular epithelium of NPs and showed that mast cells in NPs have distinct phenotypes that vary by tissue location. Glandular mast cells and the diverse subsets of mast cells detected may contribute to the pathogenesis of CRSwNP.


Treatment of Tinnitus with Intratympanic Injection of Dexamethasone Versus Oral Drugs.
Tinnitus is a symptom of cochlear dysfunction, which can disturb the patient emotionally and physically. As anxiety and tinnitus persist concurrently, certain benzodiazepines have been administered as possible tinnitus treatment options. In addition to pharmacological medications, certain studies have looked at the use of vitamins to treat tinnitus. Intratympanic steroids have been successfully used in various studies as well, for the treatment of tinnitus. A clinical based interventional study was taken up among the patients visiting the ENT OPD of a State Medical College and Hospital. 160 subjects were included in the study by convenient sampling method, taking the inclusion and the exclusion criteria into consideration. Out of them, 80 subjects were given an intratympanic injection of dexamethasone and rest 80 were given oral drugs like alprazolam and vitamin B complex. Among the patients who were treated with intratympanic dexamethasone, significant improvement was seen in 36 of them, with a p value of 0.00 as compared to those who were given oral drugs, in which only 10 showed improvement, with a p value of 0.32. The improvement of the symptoms is significantly related with the duration of the symptoms in our study. Patients presenting with severe SNHL was the commonest presentation but had the least improvement (29.6%). Patients presenting within one year of occurrence of the symptoms had maximum improvement. Intratympanic dexamethasone can be considered as a good alternative for improvement of symptoms of tinnitus.


Learning by Observing and Pitching In and the Connections to Native and Indigenous Knowledge Systems.
This chapter opens a broader dialogue of Learning by Observing and Pitching-In (LOPI) with Native and Indigenous Studies, and Native and Indigenous Education, drawing particular attention to how LOPI can provide a model for better understanding Indigenous pedagogy in Indigenous Knowledge Systems (IKS). As Battiste (2002) pointed out, "Indigenous pedagogy values a person's ability to learn independently by observing, listening, participating with a minimum of intervention and instruction." Like LOPI, IKS include ways of knowing and ways of being in the world, with life-long processes and responsibilities that model competent and respectful behavior. The chapter explores similarities and differences between IKS and LOPI by analyzing each perspective's scope, defining features, and foundational origins, as well as what each contributes to our understanding of Native and Indigenous communities, especially in terms of learning and incorporation into adulthood and family and community life.


[Electron microscopic methods for the rapid diagnosis of Q fever in animals].
Methods have been worked out for the electron-microscopic diagnosis of Q-fever. A characteristic feature with them is the use of clinical, pathological, and experimental material that is investigated through negative contrast and ultra thin sections for the detection of rickettsial cells and inclusions. It is underlined that the methods referred to are readily applicable, economic, highly effective, and hazardless. They are described for the first time and could be adopted into the diagnostic and epizootiologic practice as well as in experimental investigations.


Athanas philippei n. sp., a new alpheid shrimp associated with stomatopods in New Caledonia (Decapoda: Caridea).
A new stomatopod-associated species of the alpheid shrimp genus Athanas Leach, 1814 is described based on several specimens collected in shallow waters of northern New Caledonia. Athanas philippei n. sp. differs from all of its congeners by a unique combination of morphological characteristics, as well as a diagnostic colour pattern. All specimens of A. philippei n. sp. were collected from burrows, including one with its host, a large tiger mantis shrimp, Lysiosquillina maculata (Fabricius, 1793) (Lysiosquillidae). Thus, the new species represents the fifth species of Athanas known or presumed to be associated with the spacious burrows of stomatopods.


Methapyrilene is a genotoxic carcinogen: studies on methapyrilene and pyrilamine in the L5178Y/TK +/- mouse lymphoma assay.
Methapyrilene (MP), a sedating antihistamine, is a potent rat hepatocarcinogen which has been thought to be non-genotoxic on the basis of the negative results in a small number of short-term mutagenicity tests. The present studies show that MP is a moderately active mutagen in the L5178Y/TK +/-----TK-/- mouse lymphoma assay (MLA) in the presence of aroclor-induced rat-liver S9, and that it induces predominantly small-colony thymidine kinase-deficient (TK-/-) mutants of demonstrated chromosomal origin. 10 of 12 small colony TK-/- mutants analyzed by banded karyotype (230-band level of resolution) show aberrations to chromosome 11b, the known location of the single functional TK gene in these cells. The observed aberrations from nine of the mutants included insertions, deletions and translocations while the tenth mutant had highly rearranged, multiple copies of chromosome 11 segments. By varying the concentrations of the S9 protein and cofactors it was shown that our standard S9 composition was close to optimum for activating MP to a mutagen. The activity and stability of various lots of S9 prepared in-house or purchased from a contract laboratory revealed significant differences. The ability of 2 lots of in-house S9 to activate a standard concentration of MP increased rapidly over the first 4 weeks of liquid nitrogen storage then declined slowly over the next 16 weeks. Three separate lots of purchased S9 were essentially inactive for the first 2 weeks of liquid nitrogen storage then increased in activity thereafter; these were the only occasions in which MP was not mutagenic in our hands. The mutagenic activity of pyrilamine (PYR), a structurally related antihistamine which is far less carcinogenic in rats, but easily detected in short-term tests as being genotoxic, was also investigated in the MLA. PYR was slightly less mutagenic than MP over a comparable range of concentrations, and also induced predominantly small-colony mutants. These studies fail to adequately explain the great carcinogenic differences between these two compounds, but are consistent with the potent hepatocarcinogenicity of MP resulting through a mutagenic mechanism.


Eocene bipolar glaciation associated with global carbon cycle changes.
The transition from the extreme global warmth of the early Eocene 'greenhouse' climate approximately 55 million years ago to the present glaciated state is one of the most prominent changes in Earth's climatic evolution. It is widely accepted that large ice sheets first appeared on Antarctica approximately 34 million years ago, coincident with decreasing atmospheric carbon dioxide concentrations and a deepening of the calcite compensation depth in the world's oceans, and that glaciation in the Northern Hemisphere began much later, between 10 and 6 million years ago. Here we present records of sediment and foraminiferal geochemistry covering the greenhouse-icehouse climate transition. We report evidence for synchronous deepening and subsequent oscillations in the calcite compensation depth in the tropical Pacific and South Atlantic oceans from approximately 42 million years ago, with a permanent deepening 34 million years ago. The most prominent variations in the calcite compensation depth coincide with changes in seawater oxygen isotope ratios of up to 1.5 per mil, suggesting a lowering of global sea level through significant storage of ice in both hemispheres by at least 100 to 125 metres. Variations in benthic carbon isotope ratios of up to approximately 1.4 per mil occurred at the same time, indicating large changes in carbon cycling. We suggest that the greenhouse-icehouse transition was closely coupled to the evolution of atmospheric carbon dioxide, and that negative carbon cycle feedbacks may have prevented the permanent establishment of large ice sheets earlier than 34 million years ago.


Structural characterization and computational analysis of PDZ domains in Monosiga brevicollis.
Identification of the molecular networks that facilitated the evolution of multicellular animals from their unicellular ancestors is a fundamental problem in evolutionary cellular biology. Choanoflagellates are recognized as the closest extant nonmetazoan ancestors to animals. These unicellular eukaryotes can adopt a multicellular-like "rosette" state. Therefore, they are compelling models for the study of early multicellularity. Comparative studies revealed that a number of putative human orthologs are present in choanoflagellate genomes, suggesting that a subset of these genes were necessary for the emergence of multicellularity. However, previous work is largely based on sequence alignments alone, which does not confirm structural nor functional similarity. Here, we focus on the PDZ domain, a peptide-binding domain which plays critical roles in myriad cellular signaling networks and which underwent a gene family expansion in metazoan lineages. Using a customized sequence similarity search algorithm, we identified 178 PDZ domains in the Monosiga brevicollis proteome. This includes 11 previously unidentified sequences, which we analyzed using Rosetta and homology modeling. To assess conservation of protein structure, we solved high-resolution crystal structures of representative M. brevicollis PDZ domains that are homologous to human Dlg1 PDZ2, Dlg1 PDZ3, GIPC, and SHANK1 PDZ domains. To assess functional conservation, we calculated binding affinities for mbGIPC, mbSHANK1, mbSNX27, and mbDLG-3 PDZ domains from M. brevicollis. Overall, we find that peptide selectivity is generally conserved between these two disparate organisms, with one possible exception, mbDLG-3. Overall, our results provide novel insight into signaling pathways in a choanoflagellate model of primitive multicellularity.


Drugs to prevent vascular events after stroke.
Around 120,000 people per year in the UK have a first stroke or transient ischaemic attack (TIA). After a first stroke, about one third of people die within 1 year, and survivors remain at high risk of further vascular events (e.g. stroke myocardial infarction, vascular death). The 10-year risk of a major vascular event following minor stroke or TIA is 44%. Here we consider which drugs should be used to reduce such risks.


Radiosensitivity of head and neck cancer cells in vitro. A 96-well plate clonogenic cell assay for squamous cell carcinoma.
Radiation sensitivity was determined for nine University of Michigan squamous cell carcinoma (UM-SCC) cell lines, MCF-7 and HeLa, using a 96-well plate clonogenic assay. Plating efficiencies (PE) of the UM-SCC cell lines were between 0.16 and 0.36. Higher PE values obtained were with MCF-7 (0.4) and HeLa (0.5). The UM-SCC cell lines were used at low passages (passage 13 to passage 20) to minimize artifacts attributable to long-term culture. Cells were irradiated in suspension using a cobalt 60 gamma source at a dose rate of 0.94 Gy/min (94 rad/min). Survival data were fitted well by either a linear quadratic function F = e-(alpha D + beta D2) or by a monoexponential function F = Ae-alpha D. Mean inactivation dose, equivalent to the area under the survival curve (AUC), was used as a measure of radiation sensitivity. The UM-SCC-1, 9, 11A, 11B, MCF-7, and HeLa were the most radiation resistant lines we tested (AUC greater than 2.1), while UM-SCC-14A was the most sensitive (AUC = 1.591). The assay was highly reproducible, and the difference in radiation sensitivity between cell lines were statistically significant.


Infiltration tendency of internal mammary lymph nodes involvement in patients with breast cancer: anatomical characteristics and implications for target delineation.
Despite increasing clinical data suggest that internal mammary node (IMN) irradiation would improve local-regional control and overall survival in breast cancer, its role remains controversial due to increased risk of cardiac and pulmonary toxicity. The current study aims to determine the high risk areas of IMN metastases by collecting and analyzing the axial imaging of IMN involvement, in order to optimize IMN delineation for breast cancer. Breast cancer patients with IMN involvement were retrospectively identified from single-center database. All available imaging modalities including thoracic CT, breast MRI, ultrasound and PET/CT were used to diagnose IMN metastases. Anatomical characteristics from axial imaging, including distribution of involved ribs and distance from the internal mammary vessels (IMV), were collected for each metastatic IMN. What's more,the natural infiltration tendency of IMNs from IMV was calculated in this study. In total, 83 metastatic IMNs from 70 breast cancer patients (initial diagnosed:34 and recurrence: 36) were located from axial CT image in this study. The second intercostal space was the most likely involved in patients with single(n = 35, 53.0%) and multiple intercostal space (n = 31, 47.0%) involvement. The percentage of including IMN with a 5 mm, 6 mm and 7 mm medial/lateral distance to the IMV were 75.9% (63/83), 89.2.6% (74/83) and 92.3% (77/83) respectively. While in maximal dorsal/ventral distance, nearly 95% of the nodes were encompassed into 6 mm depth to the IMV. Over 65% of IMN adenopathy (32/49,65.3%) were found to have a growth direction close to the sternum. By retrospective reviewing diagnostic reports, MRI demonstrated a high diagnostic performance in diagnosis of IMN disease (90.3%, 28/31), while CT had a higher misdiagnosis rate (22/63, 34.9%). The diagnostic efficiency of IMN could be improved if different methods were combined. For patients with indications of prophylactic IMN irradiation, a 7 mm medial and 6 mm dorsal distance to the IMV on axial CT would be optimal to cover the clinical volume of IMN; and it would be reasonable to extend clinical tumor volume (CTV) coverage towards sternum for patients with evident IMN disease. Multi-imaging modalities are recommended to improve the diagnostic specificity and sensitivity of IMN metastases.


[Preliminary study of fetal head engagement diagnosis by transperineal ultrasound before operative vaginal delivery].
Estimate the predictive value of perineum-fetal head distance obtained by transperineal ultrasound on results of an operative vaginal delivery. A prospective preliminary monocentric study has been conducted on 28 patients between the 18th of April and the 31st of July 2011. Three successive perineum-fetal head distance have been measured before realization of an operative vaginal delivery. With caesarian section deliveries, average distances were higher than with successful operative vaginal deliveries but this result was not significant (49.3mm vs 39.7 mm; P=NS). Ultrasound measured distance was significantly correlated to the time of application of the instrument (r=0.45, P=0.0165). Beyond 50mm, the relative risk of caesarian was 10.5 (IC [0.76-145.36]). The measures were corresponding, with an average time of realization of 29.9 seconds. The transvaginal examination compared to ultrasound showed a discordance of 3.6% for the diagnosis of engagement and of 25% for the descent of fetal head. A larger study is necessary to confirm this result and to recommend the realization of a transperineal ultrasound before an operative vaginal delivery in cases of doubt about engagement after the transvaginal examination.


Kefir consumption does not alter plasma lipid levels or cholesterol fractional synthesis rates relative to milk in hyperlipidemic men: a randomized controlled trial [ISRCTN10820810].
Fermented milk products have been shown to affect serum cholesterol concentrations in humans. Kefir, a fermented milk product, has been traditionally consumed for its potential health benefits but has to date not been studied for its hypocholesterolemic properties. Thirteen healthy mildly hypercholesterolemic male subjects consumed a dairy supplement in randomized crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy supplement consumed. Blood samples were collected at baseline and after 4 wk of supplementation for measurement of plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride concentrations, as well as fatty acid profile and cholesterol synthesis rate. Fecal samples were collected at baseline and after 2 and 4 wk of supplementation for determination of fecal short chain fatty acid level and bacterial content. Kefir had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglyceride concentrations nor on cholesterol fractional synthesis rates after 4 wk of supplementation. No significant change on plasma fatty acid levels was observed with diet. However, both kefir and milk increased (p < 0.05) fecal isobutyric, isovaleric and propionic acids as well as the total amount of fecal short chain fatty acids. Kefir supplementation resulted in increased fecal bacterial content in the majority of the subjects. Since kefir consumption did not result in lowered plasma lipid concentrations, the results of this study do not support consumption of kefir as a cholesterol-lowering agent.


Tissue reactions around two alloplastic ligament substitute materials: experimental study on rats with carbon fibres and polypropylene.
The early connective tissue reactions around two alloplastic and prosthetic materials, carbon fibre and polypropylene were examined in 30 rats. Each of the materials was implanted into three sites: under the skin, intraperitoneally and into a femoral bone tunnel. Microscopic and scanning electron microscopic findings at 1, 3, 6, 9 and 12 wk post-operatively are described. The amount of granulation tissue around the carbon fibres was more prominent in all the environments, but the connective tissue remained less mature and less organized during the whole follow-up compared to that of the polypropylene. There was no ingrowth of bone between the bundles of the artificial materials in the bony tunnels. The differences in the early cellular reactions and scar tissue maturation in the interstices of these two materials are probably due to the structural differences rather than to the surface properties of the materials.


Evaluation of Patients with Sinonasal and Ventral Skull Base Malignancies.
A wide variety of tumors present in the sinonasal and ventral skull base. Patients often have nonspecific symptoms initially and present with advanced tumors, affecting the orbit and other adjacent structures. Evaluation of these malignancies with modern imaging techniques can define tumor invasion, but biopsy is often required to establish a diagnosis because most have a nonspecific appearance. A thorough understanding of the anatomy is the key to treatment planning, and a multidisciplinary approach determines the optimal strategy.


Quantification of bovine plasma amino acids via liquid chromatography-electrospray ionization-mass spectrometry: Comparison of underivatized and precolumn derivatized methods.
The objectives of this experiment were to evaluate and compare underivatized (UND) and precolumn derivatized (DER) methods for quantification of bovine plasma AA by isotope dilution ratio via liquid chromatography-electrospray ionization (ESI)-single quadrupole mass spectrometry. Linearity of the mass-to-charge ratio signal and area signal sensitivity of 12C were evaluated for each AA with 5-point standard curves (range: 1.1-500 µM). Plasma from lactating dairy cows was isolated by centrifugation and deproteinized using 1 N perchloric acid with a final concentration of 0.5 N. Deproteinized plasma was filtered and injected into a 50 × 2-mm column (Imtakt) or extracted, derivatized, and injected into a 250 × 3-mm column (EZ:faast, Phenomenex) and analyzed via liquid chromatography-ESI-single quadrupole mass spectrometry. Coefficients of variation and recovery rates were evaluated using 4 replicates of pooled plasma samples spiked with each AA at concentrations of 10, 20, and 50 µM. In addition, a subset of 24 plasma samples was used to directly compare methods using linear regression, correlation coefficient (r), concordance correlation coefficient (CCC), and Bland-Altman plot test. Both methods showed linearity within the dynamic range analyzed for all essential AA (coefficient of determination, R2 ≥ 0.995) and most other AA, although the UND samples had poor linearity (R2 ≤ 0.990) or peak resolution problems for Asp, Gly, Tyr, and Ser. Moreover, area signal sensitivity for 12C AA was greater for DER samples than for UND samples [range: 2.2× (Pro) to 309.5× (Ala)]. Both methods had recovery rates ranging from 85.7 to 119.8.0%, and none differed from 100% except Gln [20 µM (85.7%) and 50 µM (87.6%)] and Val [50 µM (119.8%)] using the UND method. The UND method had a coefficient of variation ranging from 0.9% (Val) to 7.8% (His), whereas for the DER method the range was 2.2% (Glu) to 8.8% (Asp). The highest correlation coefficient (>0.90) and CCC (>0.90) were observed for Arg, Ile, Leu, Met, Thr, Trp, Val, and Gln, with the Bland-Altman plot test showing minimal mean bias for these AA. Lowest values were observed for His (r = 0.46; CCC = 0.45), Lys (r = 0.76; CCC = 0.75), Ala (r = 0.83; CCC = 0.73), and Glu (r = 0.65; CCC = 0.42). The UND method showed linearity, precision, and accurate recovery rates for most AA, with most essential AA having comparable values between the 2 methods. However, the DER method had greater 12C AA area signal sensitivity, linearity, and recovery rates.


VA community mental health service providers' utilization of and attitudes toward telemental health care: the gatekeeper's perspective.
Mental health (MH) providers in community-based outpatient clinics (CBOCs) are important stakeholders in the development of the Veterans Health Administration (VA) telemental health (TMH) system, but their perceptions of these technologies have not been systematically examined. The purpose of this study was to investigate the attitudes of CBOC providers about TMH services, current utilization of these technologies in their clinics, and sources of knowledge regarding TMH. The study employed a mixed-methods design to examine aspects of TMH in CBOCs located in a VA network in the south-central United States. Semistructured, on-site group interviews conducted with 86 CBOC MH providers were followed by in-depth phone surveys with an MH provider identified as a key informant at each of 36 CBOCs in the VA network. The utilization of TMH services varied widely between CBOCs, and the scope of services provided typically focused on delivery of medication management, with little provision of psychological services. Further, several important barriers to expanded use of TMH were identified, including limited education and training and shortage of dedicated space for TMH encounters. General attitudes toward TMH were positive, and most CBOC providers indicated that they would like to expand use of TMH in their clinics.


Nasal airflow and resistance measured by active anterior rhinomanometry in healthy children and adolescents.
Rhinomanometry allows objective assessment of nasal patency in pediatric patients with nasal and other respiratory problems. However, no reliable reference values are available in the pediatric age group. We measured nasal inspiratory airflow and nasal inspiratory resistance of the right and left nostrils (V'nar, V'nal, Rnar, and Rnal) and total nasal inspiratory flow and resistance (V'na and Rna) at a transnasal pressure of 150 Pa during quiet breathing in healthy children with a closed mouth by using active anterior rhinomanometry. Cross-sectional measurements were done in 192 healthy Caucasian children and adolescents free of nasal or other respiratory diseases (age, 2-19 years; body height, 94-190 cm; 95 boys and 97 girls). The values of V'na, V'nar, and V'nal increased significantly with an increase of body height or age (P<0.0001). Rna, Rnar, and Rnal significantly decreased with an increase of body height and age (P<0.0001). No significant statistical differences were found between boys and girls (P=0.11) or between right and left nostrils (P=0.07). V'nar and Rnar comprised 50.1%, and V'nal and Rnal 49.9%, of total V'na and Rna, respectively. Best-fit regression equations relating rhinomanometric parameters and body height or age were power functions. We obtained reference regression equations with upper and lower limits, and prepared tables listing reference (normal) values of rhinomanometric parameters in healthy pediatric Caucasian patients, against which patients with nasal obstruction can be compared.