Population pharmacokinetics of mizoribine in pediatric recipients of renal transplantation.
An immunosuppressive agent, mizoribine, is excreted predominantly in the urine. The aim of this study was to investigate the pharmacokinetic variability of mizoribine in pediatric recipients of renal transplantation. Pharmacokinetic data for population analysis were collected from 51 recipients (32 males and 19 females) treated with oral administration of mizoribine (0.83-5.56 mg/day/kg). The population pharmacokinetic parameters of mizoribine were estimated using a nonlinear mixed effects model program. The pharmacokinetics of mizoribine in pediatric recipients of renal transplantation was well described by a one-compartment model with first-order absorption. The mean value of the absorption lag time (ALAG) and absorption rate constant (K (A)) was estimated to be 0.363 h and 0.554 h(-1), respectively. Apparent volume of distribution (V/F) was modeled as a function of body weight (WT), and the mean value was estimated to be 1.03 · WT L. Oral clearance (CL/F) was modeled as a function of creatinine clearance (CL(cr)), and the mean value was estimated to be 2.81 · CL(cr) · 60/1000 L/h. In addition, there was a positive correlation between CL(cr)-corrected CL/F and WT-corrected V/F in the pediatric recipients, indicating large interindividual variability in the bioavailability (F) of mizoribine. The present findings indicated that the rate of renal excretion and also the extent of intestinal absorption of mizoribine are responsible for the large interindividual pharmacokinetic variability of the drug.


Impact of mycophenolate mofetil dose posttransplantation on 12-month renal function: analysis of the MOST database.
Mycophenolate mofetil (MMF) has greatly reduced the risk of acute rejection episodes (ARE) after renal transplantation, but dose reductions/withdrawals could jeopardize long-term results. The MOST database of "de novo" patients treated with MMF at month 1 and functioning grafts at month 12 were divided into 2 groups: groups 1, 2 g MMF at month 1 and month 12; and group 2, 2 g MMF at month 1 but MMF <2 g at month 12 to evaluate renal function glonerular filtration rate (GFR). In this study, 1136 patients were receiving 2 g MMF at month 1. On month 12, 645 were on 2 g (56.8%, group 1) and 431 were on <2 g (43.2%, group 2). Group 1 included younger recipients of younger donors with fewer patients with delayed graft function (DGF). Group 1 showed more ARE during month 1 and more patients who received induction. Mean Neoral daily doses at month 1/month 12 were 5.3/3.0 and 5.3/3.1 mg/kg in group 1 and group 2, respectively (P = .05 at month 12). GFR in group 1 and group 2 were 59.06 (CI 57.10-60.60) and 53.81 (CI 52-55.7) at month 1 (P < .001); 63.7 (CI 62.1-65.30) and 55.9 (CI 54.1-57.7) mL/min*1.73 m(2) at month 12 (P < .001). The mean increases in GFR between month 1 and month 12 were 4.64 and 1.94 mL/min*1.73 m(2), respectively (P < .05). A multivariate analysis also included 795 patients from the "maintenance" patient database with retrospective detailed information. The following parameters were highly predictive for good renal function at month 12: donor age younger than 60 years, recipient age younger than 60 years, immediate graft function, 12-month MMF dose = 2 g, absence of CMV infection, and 12-month Neoral dose <3 mg/kg/d. Maintenance of MMF dose at 2 g/d during the first year appears to facilitate the attainment of optimal renal function at 12-months after kidney transplantation.


Radiometric assessment of experimental autoimmune encephalomyelitis in mice.
The cell-mediated inflammatory component of experimental autoimmune encephalomyelitis (EAE) in mice is measured by the radioisotopic technique. Mice are challenged with autologous spinal cord homogenate in Freund's complete adjuvant and at various time intervals after such immunization given [125I]5-iodo-2'-deoxyuridine which is incorporated into the mononuclear cell pool. The degree of cell-mediated inflammation is determined by radiometry of the brain and spinal cord tissues. Increased radiolabelling is detected in the brains 2 days prior to the onset of clinical signs of EAE; increased radioactivity of the spinal cord is concomitant with clinical signs. This technique is useful in staging the extent of EAE and may prove to be a powerful tool in studying cell-mediated reactions in other autoimmune diseases.


Optimized isolation of 7,7'-biphyscion starting from Cortinarius rubrophyllus, a chemically unexplored fungal species rich in photosensitizers.
Mushrooms such as the dermocyboid Cortinarius rubrophyllus are characterized by strikingly colorful fruiting bodies. The molecular dyes responsible for such colors recently experienced a comeback as photoactive compounds with remarkable photophysical and photobiological properties. One of them-7,7'-biphyscion-is a dimeric anthraquinone that showed promising anticancer effects in the low nanomolar range under blue-light irradiation. Compared to acidic anthraquinones, 7,7'-biphyscion was more efficiently taken up by cells and induced apoptosis after photoactivation. However, seasonal collection of mushrooms producing this compound, low extraction yields, and tricky fungal identification hamper further developments to the clinics. To bypass these limitations, we demonstrate here an alternative approach utilizing a precursor of 7,7'-biphyscion, i.e., the pre-anthraquinone flavomannin-6,6'-dimethyl ether, which is abundant in many species of the subgenus Dermocybe. Controlled oxidation of the crude extract significantly increased the yield of 7,7'-biphyscion by 100%, which eased the isolation process. We also present the mycochemical and photobiological characterization of the yet chemically undescribed species, i.e. C. rubrophyllus. In total, eight pigments (1-8) were isolated, including two new glycosylated anthraquinones (1 and 2). Light-dependent generation of singlet oxygen was detected for the first time for emodin-1-O-β-D-glucopyranoside (3) [photophysical measurement: Φ∆ = 0.11 (CD3OD)]. Furthermore, emodin (7) was characterized as promising compound in the photocytotoxicity assay with EC50-values in the low micromolar range under irradiation against cells of the cancer cell lines AGS, A549, and T24.


Fecal protoporphyrin excretion in erythropoietic protoporphyria: effect of cholestyramine and bile acid feeding.
The effect of cholestyramine and bile acid feeding upon fecal, red blood cell, and plasma protoporphyrin levels was evaluated in a patient with erythropoietic protoporphyria and evidence of hepatic damage. After a basal period on a controlled diet, bile acids alone were administered (300-900 mg) daily for 9 days, followed by cholestyramine (12 g) plus bile acids (900 mg) daily for 7 days, and cholestyramine alone (12 g) daily for 6 days. There was no substantial change in either the red blood cell or plasma protoporphyrin concentrations during any treatment period. However, cholestyramine and cholestyramine combined with bile acids caused a threefold increase in fecal protoporphyrin excretion, whereas bile acids alone had no effect in this regard. After 1 yr of cholestyramine therapy, fecal excretion of protoporphyrin remained elevated with concurrent improvement in liver function tests and photosensitivity. This study indicates that cholestyramine but not bile acids can substantially increase protoporphyrin excretion and therefore may be capable of ameliorating the hepatotoxicity that may occur in selected patients with erythropoietic protoporphyria.


Determinants of acute hospital care use by elderly patients in Italy from 1996 to 2006.
To determine the trend of elderly hospitalization rates in Italy, following the economic rationalization of health systems in Western countries, and to evaluate which alternatives to acute hospitalization have been developed during the period 1996-2006 an ecological observational study has been carried out. Data from the Italian Hospital-Discharge Registries (HDRs) of the years 1996, 2001, and 2006 have been analyzed in order to assess the variations among the elderly in terms of hospitalization rates, hospital stay, and bed rates. The results were compared with nursing home admission rates and home care offer. Relations among these variables were explored by univariate and multivariate analyses. Elderly hospital admission rates decreased in Italy from 324.2/1000 in 1996, to 258.7 in 2006. Mean hospital stay of elderly patients was 9.4 days in 2006, 9.5 in 2001 and 10.1 in 1996. A multivariate linear regression model was statistically significant in explaining the variations in hospitalization rates (F: 5.68; p=0.004; R(2)=0.77). The main determinants linked to such variations were the bed rate (β=0.67; p=0.004) and the hospital length of stay (β=-0.77; p=0.03). The analysis showed a reduction in hospitalization rates among the elderly, which was not counterbalanced by an increased offer of home care and/or nursing home services, but was mainly linked to a decrease in the supply of acute beds, with possible consequences on the quality of health care.


[Electrical model of the electroreceptor of the ampulla of Lorenzini].
An electrical model is proposed for the Lorenzinian ampulla receptor epithelium. The model is based on the authors' experimental results and explains most of the experimental data available in literature, including an unusual sign of spike response in afferent fibres and complex patterns of electroreceptor responses to the applied stimuli. Its main assumption is an N-shaped voltage-current relation of the receptor cell apical membrane possessing, within the range of operation, a stationary negative-slope resistance.


Antilung cancer activities of selenium.
Selenium is considered an essential trace element in most animal and plant species, although still reported in many texts as a highly toxic material. Epidemiological investigations have reported an inverse relationship between selenium and lung cancer. Explanations of reported observations have resulted in numerous mechanistic theories. Only recently have selenium metabolites involved in excretion been considered potential agents for antilung cancer activity. Anticancer properties have been shown in occupationally exposed copper smelter workers, dietary investigations and experimental studies. Supplementation with selenium of public water supplies, as is currently done with fluoride, is a potential method for increasing the blood concentration. This may permit development of a population prevention strategy against lung cancer and other diseases.


Thrombin generation in vivo and ex vivo in sickle cell disease patients.
Activation of coagulation is an important hallmark of sickle cell disease (SCD) and it is believed that hypercoagulability plays a role to the disease pathophysiology. Studies have sought to identify how hemostatic biomarkers are expressed in SCD, however, the results are inconclusive. In this context, our objective was to evaluate the thrombin generation in vivo and ex vivo in SCD patients and the association between these biomarkers and the use of HU. This cross-sectional study was carried out with patients diagnosed with SCD, users or not of Hydroxyurea (HU), and healthy individuals as controls. D dimer (D-Di) was evaluated by ELISA and (TGT) thrombin generation test by CAT method. D-Di plasma levels were significantly higher in SCD patients when compared to the controls. TGT parameters such as peak, ETP and normalized ETP at low TF concentration and time-to-peak, peak, ETP and normalized ETP values at high TF concentration were lower in SCD patients than in controls. In contrast, the normalized activated protein C sensitivity ratio (nAPCsr) was higher in patients compared to controls, indicating resistance to the action of this natural anticoagulant. Regarding the use of HU, comparing users and non-users of this drug, no difference was observed in D-Di levels and in most TGT parameters. Our data analyzed together allow us to conclude that patients with SCD present a state of hypercoagulability in vivo due to the higher levels of D-Di and resistance to APC assessed ex vivo which is consistent with the coagulation imbalance described in SCD patients.


Volume homeostasis in normal and hypertensive human pregnancy.
In this chapter are outlined the many factors involved in the regulation of sodium and volume homeostasis in normal human pregnancy and their interrelationships. New developments concerning the role of sodium/potassium ATPase, atrial natriuretic peptide, arginine vasopressin and angiotensin II as regulatory forces are outlined, together with a review of earlier work. Abnormalities found in women with, or destined for, PAH are described and their significance is discussed.


The pharmacokinetics and efficacy of long-term low-level and split-dose administration of albendazole through in-feed formulations against ovine and caprine parasitic gastroenteritis.
Two trials were conducted against natural and experimentally induced parasitic gastroenteritis in sheep and goats using an in-feed formulation of albendazole to evaluate its therapeutic and prophylactic efficacy. In the first trial, albendazole was incorporated in feed pellets to deliver an average daily dose of 0.7 mg/kg body weight in order to evaluate its prophylactic efficacy. In the second trial, feed pellets were offered to deliver an average total dose of 8.0 mg/kg body weight in two equal split doses in order to evaluate its curative efficacy. Sustained plasma concentrations of the active compound, albendazole sulphoxide, and its metabolite albendazole sulphone, sufficient to prevent establishment of infection, were achieved when the animals were allowed to feed on medicated pellets for 10 consecutive days. The bioavailability of the metabolites of albendazole following the administration of a therapeutic dose in two split doses of the in-feed formulation was sufficient to remove established adult nematodes. The concentrate feed pellets could be used for self-medicating small ruminants for therapeutic use as well as for prophylaxis based on their strategic use appropriate to the epidemiology of the parasitic disease.


Vitamin D receptor ApaI (rs7975232), BsmI (rs1544410), Fok1 (rs2228570), and TaqI (rs731236) gene polymorphisms and susceptibility to pulmonary tuberculosis in an Iranian population: A systematic review and meta-analysis.
Polymorphisms of vitamin D receptors (VDRs), ApaI, BsmI, FokI, and TaqI might affect susceptibility to tuberculosis (TB). In this systematic review and meta-analysis, all published articles which investigated the effects of these polymorphisms on the risk of TB in the Iranian population were retrieved. PubMed and Scopus were searched with no date or language restrictions. In this meta-analysis, the Comprehensive Meta-Analysis (CMA) version 2.0 and random effects model were applied. The association of polymorphisms with TB risk was assessed by measuring the odds ratio (ORs) at 95% CI. Heterogeneity was investigated based on Cochran Q-test and I2-index statistics. The significance level was set at 0.05. Also, Egger's regression intercept was determined to measure publication bias. A total of six articles on Iranian populations were included. TaqI (5/6 included studies) showed a significant association with the increased risk of TB based on ORs (allele comparison: 1.57 (1.0, 2.3), p-value: 0.02; additive model of tt/TT: 1.57 (0.9, 2.5), p-value: 0.05; recessive model (tt/Tt + TT): 1.99 (1.2, 3.2), p-value: 0.00; dominant model (tt + Tt/TT): 1.98 (1.1, 3.5), p-value: 0.01). BsmI showed a significant positive effect on TB risk only in its dominant genotype (bb + bB/BB) (1.44 (1.0, 1.9); p-value: 0.02). FokI and ApaI did not show any significant effects on TB development in Iranian populations. Findings showed the significant effect of TaqI polymorphism in all genetic models and the dominant model of BsmI on the increased risk of TB. However, the effects of TaqI and BsmI should be further investigated in a larger sample size.


Ultrasound directed extrahepatic bile duct intraluminal brachytherapy.
Intraluminal brachytherapy with a transcatheter Iridium-192 (Ir-192) wire, as a method to deliver a boost to patients with tumors of the extrahepatic bile ducts, has been well described. A major limitation of current imaging techniques is the inability to accurately define the proximal, distal, and most importantly the lateral extent of the tumor. We have found endoluminal ultrasound, which to this date has been used primarily to measure arterial wall layers, can successfully determine tumor volume in the bile ducts. The small diameter of these ultrasound probes allows easy insertion into a biliary duct drainage tube. Given the uncertainties in the determination of tumor size in the bile ducts, ultrasound is an ideal method by which to obtain the measurements. We present a case of recurrent islet cell carcinoma treated with external beam radiation therapy and an Ir-192 intraluminal brachytherapy boost in which the ultrasound probe was used to determine the tumor volume and response to therapy.


Intramedullary spinal cord tumors in children.
Pediatric intramedullary spinal cord tumors are rare and make up only a small percentage of all central nervous system neoplasms. These neoplasms are predominantly benign histologically, regardless of size, with a large percentage being astrocytomas or gangliogliomas. Ependymomas, which are common in adults, are relatively uncommon in children. Contemporary management of these tumors has generated much controversy. These neoplasms occur primarily in the cervical region, with pain or a motor deficit as the chief complaint. Surgery on these neoplasms can safely be performed using modern surgical adjuncts such as the ultrasonic aspirator, contact laser and neurophysiological monitoring. A radical resection of these tumors results in a good long-term outcome, since the majority are histologically benign. Adjuvant radiation therapy should only be administered for high-grade or malignant tumors. The majority of spinal cord tumors are benign; however, malignant tumors have a dismal outcome and surgery in these children should be limited to a conservative debulking. An attempt should be made for radical surgery in hope of avoiding radiation and chemotherapy for the benign tumors. Spinal deformity is a concern in these patients since 35% of children may require a stabilization procedure.


Efficacy and safety of albendazole against experimentally induced Fasciola hepatica infections in goats.
Forty 8-week-old goats were allocated to five groups of equal size to determine the optimal dosage of albendazole against experimentally induced 14-week-old Fasciola hepatica infections. Albendazole suspension given orally at 5.0, 7.5, 10.0 and 15 mg kg-1 of body weight was 73.3, 88.2, 88.3 and 95.9% effective, respectively, when compared to untreated controls. Mean number of F. hepatica in the untreated control goats was 75.4. No signs of toxicity were observed. When albendazole was given to eight, 8-week-old goats orally at 75 mg kg-1 (five times the optimal dosage), no signs of toxicity were observed.


Novel biologically active nitro and amino substituted benzimidazo[1,2-a]quinolines.
This manuscript described the synthesis and biological activity of novel nitro substituted E-2-styryl-benzimidazoles and E-2-(2-benzimidazolyl)-3-phenylacrylonitriles and nitro and amino substituted benzimidazo[1,2-a]quinolines (4-5, 6-11, 17-20, and 21-32). All of the compounds showed significant growth inhibitory effect towards five tumor cell lines, whereby the IC(50) concentrations of 11, 20, 28, 29, 30, 32 are in the low micromolar range (IC(50)=2-19 μM). The DNA binding experiments did not show significant affinity of two selected compounds towards ct-DNA. The flow cytometry analysis of potential cell cycle perturbations after the treatment with compounds 9, 11, 25, and 29 demonstrated that all of the compounds (5 μM ≈ IC(50)) significantly delayed the progression through G1 phase, as demonstrated by the accumulation of cells in G1 phase, accompanied with the reduction of the cell number in the cells in S phase, which does not point to DNA damage as the main mechanism of action. Also, fluorescence microscopy study showed cytoplasmic distribution of the compounds, demonstrating that DNA is not the primary target of compounds. Thus, considerable antiproliferative effects of studied compounds are due to interactions with other biological targets within cells.


Localized vessel expression of lipoprotein lipase in rabbits leads to rapid lipid deposition in the balloon-injured arterial wall.
Recent studies on mice demonstrated that lipoprotein lipase (LPL) located in the arterial wall might play a pro-atherogenic role. There are major differences between humans and mice in lipoprotein metabolism and in susceptibility to atherosclerosis. We have therefore used rabbits fed normal chow diet as a model to assess such localized effects by adenovirus-mediated gene transfer of human catalytically active wild type LPL (hLPLwt) and an inactive mutant (hLPL194) to balloon-injured carotid arteries. By morphometric analysis on cryosections stained with Oil Red O (ORO) we found 7- and 4-fold increases, respectively, of lipid deposition in the arterial walls 7 days after infection with adenovirus expressing hLPLwt or hLPL194, when compared with a virus expressing human alkaline phosphatase (hAP) as control. Macrophages were detected in the arteries expressing both forms of LPL, but apoB was only found in arteries expressing hLPLwt. Expression of the LPL gene products was transient and was gone after 2 weeks, but the accumulated lipid deposits remained between the neointimal and the media layers even after 8 weeks. Our data demonstrate that expression of LPL in the arterial wall (with or without lipase activity) leads to lipid accumulation in balloon-injured rabbit arteries, and could result in enhanced formation of atherosclerotic lesions.


Arf1p, Chs5p and the ChAPs are required for export of specialized cargo from the Golgi.
In Saccharomyces cerevisiae, the synthesis of chitin is temporally and spatially regulated through the transport of Chs3p (chitin synthase III) to the plasma membrane in the bud neck region. Traffic of Chs3p from the trans-Golgi network (TGN)/early endosome to the plasma membrane requires the function of Chs5p and Chs6p. Chs6p belongs to a family of four proteins that we have named ChAPs for Chs5p-Arf1p-binding Proteins. Here, we show that all ChAPs physically interact not only with Chs5p but also with the small GTPase Arf1p. A short sequence at the C-terminus of the ChAPs is required for protein function and the ability to bind to Chs5p. Simultaneous disruption of two members, Deltabud7 and Deltabch1, phenocopies a Deltachs6 or Deltachs5 deletion with respect to Chs3p transport. Moreover, the ChAPs interact with each other and can form complexes. In addition, they are all at least partially localized to the TGN in a Chs5p-dependent manner. Most importantly, several ChAPs can interact physically with Chs3p. We propose that the ChAPs facilitate export of cargo out of the Golgi.


Perceptions on radioprotective garment usage and underlying reasons for non-adherence among medical radiation workers from public hospitals in a middle-income Asian setting: A qualitative exploration.
Radioprotective garments protect medical radiation workers from exposure to radiation at workplace. However, previous studies have found poor adherence to the use of radioprotective garments. We explored the perceptions and practices related to the use of radioprotective garments among medical radiation workers in public hospitals, and sought to understand the reasons for non-adherence. A qualitative approach was applied by conducting face-to-face in-depth interviews with 18 medical radiation workers from three university hospitals using a semi-structured interview guide. Five themes emerged with respect to perceptions on the use of radioprotective garments: (i) the dilemmas in practising radiation protection, (ii) indication of workers' credibility, (iii) physical appearance of radioprotective garments, (iv) practicality of radioprotective garment use, and (v) impact on workflow. Actual lack of radioprotective garment use was attributed to inadequate number of thyroid shield and other garments, radioprotective garments' unsightly appearance including being dirty and defective, impracticality of using radioprotective garments for some nuclear medicine procedures, disruption of workflow because of workers' limited movements, attitudes of workers, and organisational influences. Medical radiation workers demonstrated a definitive practice of using radioprotective aprons, but often neglected to use thyroid shields and other garments. Availability and hygiene are reported as the core issues, while unclear guidelines on practical use of radioprotective garments appear to lead to confusion among medical radiation workers. To the best of our knowledge, this is the first qualitative study of its kind from a middle-income Asian setting.


Binding of epithelial cells to lectin-coated surfaces.
Epithelial cells may relate to their basement membrane substrates via lectin-like interactions. In a model system for study of this type of interaction, lectin-coated bacteriological plastic petri dishes were presented as substrates for epithelial cell adhesion. Of 21 lectins tested by mixed agglutination against two epithelial cell types, Madin-Darby canine kidney (MDCK), and human embryonic kidney cells (HEK), nine gave less than 5% rosettes and 12 gave 5 to 50% rosettes. Wheat germ agglutinin (WGA) and Geodia cydonium lectin gave the highest percentage of rosettes. Wheat germ agglutinin was readily adsorbed to plastic surfaces and maintained specificity in binding interactions. Both MDCK and HEK cells attached as well to WGA coated petri dishes as to conventional tissue culture dishes. Furthermore, both spread over the lectin-coated surfaces. The MDCK cells grew to confluence and could be subcultured and maintained indefinitely on such surfaces, although WGA in solution was toxic to the cells in concentrations as low as 0.1 to 1.0 microgram/ml. Cell attachment to WGA coated dishes was blocked by cycloheximide only if the cells had been preincubated with the inhibitor for several hours. Cell attachment was not inhibited by pretreatment of cells with neuraminidase. Precoating cells with WGA blocked binding to both WGA-coated surfaces and untreated tissue culture dishes. Cells attached to WGA-coated dishes could not be readily dislodged by trypsin-EDTA for the first 2 h after subculture. By 4 h, attachment was again trypsin sensitive, suggesting that the cells synthesized a trypsin-sensitive material that was laid down between the cell surface and the WGA-coated dish. Regeneration of trypsin sensitivity was not blocked by cycloheximide.


A prospective crossover trial of botulinum toxin chemodenervation versus injection augmentation for essential voice tremor.
Botulinum toxin chemodenervation (BTX) is used to treat essential voice tremor (EVT), but results are not uniformly satisfactory. This study sought to assess the comparative utility of injection augmentation (IA) for EVT. Prospective crossover treatment study. Patients with EVT underwent BTX. After washout patients underwent IA. Multidimensional assessment carried out prior to and 30 days after each treatment included 1) videostroboscopy graded by the Vocal Tremor Scoring System (VTSS), 2) acoustic and aerodynamic assessment (cepstral peak prominence, cepstral spectral index of dysphonia, cepstral peak prominence fundamental frequency, airflow, peak air pressure and intensity, maximum phonation time, and amplitude/frequency of tremor), 3) audio-perceptual assessment via Consensus Audio-Perceptual Evaluation of Voice (CAPE-V), and 4) patient self-assessment via Voice Handicap Index-10 (VHI-10) and Percent of Normal Function (PNF) scale. Findings were analyzed via paired t tests and Wilcoxon rank sum tests. Seven patients (five female and two male; mean age 67 years old; range, 46-82 years old) participated. VTSS grading showed divergent outcomes for certain individual sites of tremor, but without significant differences. Airflow increased following BTX and decreased following IA, and VHI-10 scores indicated slight improvement post-BTX (26.29-23.57), and decline post-IA (25.86-29.86), although differences were not significant. Only changes in audio-perceptual ratings of loudness achieved significance, which decreased with BTX and increased with IA. Five patients chose to resume BTX; two elected long-term IA. No findings supported patient preferences. IA demonstrated no advantage over BTX in the treatment of EVT. 2b. Laryngoscope, 128:437-446, 2018.


Differential changes in gene expression in rainbow trout hepatocytes exposed to extracts of oil sands process-affected water and the Athabasca River.
The oil sands region of northern Alberta represents the world's largest reserves of bitumen, and the accelerated pace of industrial extraction activity has raised concern about the possible impacts on the Athabasca River and its tributaries. An ecotoxicogenomic study was undertaken on Oncorhynchus mykiss trout hepatocytes exposed to extracts of water samples near the oil sand development area, as well as to oil sands process-affected water (OSPW) extracts using the quantitative reverse transcriptase polymerase chain reaction technique. The expression of the following genes (mRNA) was monitored to track changes in xenobiotic biotransformation (CYP1A1, CYP3A4, glutathione S-transferase, multi-drug resistance transporter), estrogenicity (estrogen receptor and vitellogenin), oxidative stress (superoxide dismutase and metallothionein) and DNA repair activity (DNA ligase). The extent of DNA-aromatic hydrocarbon adducts was also determined in cells by immuno-staining. A comparative analysis of gene expression between the river/lake and OSPW samples revealed that CYP3A4, metallothioneins, DNA ligase and GST genes, were specifically expressed by OSPW. Cells exposed to OSPW, commercial naphthenic acids, and benzo(a)pyrene showed increased polyaromatic hydrocarbon DNA-adducts, as determined by cell immunofluorescence analysis. Other genes were induced by all types of water samples, although the induction potential was stronger in OSPW most of the time (e.g., VTG gene was expressed nearly 15-fold by surface waters from the lake and river samples but increased to a maximum of 31-fold in OSPW). A multivariate discriminant function analysis revealed that the lake and river water samples were well discriminated from the OSPW. The CYP3A4 gene was the most highly expressed gene in cells exposed to OSPW and responded less to the lake or river water in the Athabasca River area. This study identified a suite of gene targets that responded specifically to OSPW extracts, which could serve as toxicogenomic fingerprints of OSPW contamination.


The effects of frontal EMG biofeedback and progressive relaxation upon hyperactivity and its behavioral concomitants.
Hyperactive children (N = 15) and nonhyperactive children (N = 15) were compared. Hyperactive children were found to possess significantly higher (p less than .002) muscular tension levels and, in addition, presented more behavioral problems and had lower test scores. Both electromyographic (EMG) biofeedback and progressive relaxation exercises were successful in the significant reduction of muscular tension, hyperactivity, distractability, irritability, impulsivity, explosiveness, aggressivity, and emotionality in hyperactive children. The greatest improvement was seen in the area of "emotionality-aggression" (irritability, explosiveness, impulsivity, low frustration tolerance, aggresion). No differences were seen in the EMG improvement of drug and nondrug hyperactive children; both made progress under these self-control techniques. However, nondrug children made greater improvements in the behavioral area. Both EMG biofeedback and progressive relaxation resulted in improvements on the test scores of hyperactive subjects (Bender-Gestalt, Visual Sequential Memory, Digit Span, Coding). The therapy would appear to be improved by the inclusion of mental relaxation, concentration, meditation, and mind-blanking exercises for mental control.


Muscle cells provide instructions for planarian regeneration.
Regeneration requires both potential and instructions for tissue replacement. In planarians, pluripotent stem cells have the potential to produce all new tissue. The identities of the cells that provide regeneration instructions are unknown. Here, we report that position control genes (PCGs) that control regeneration and tissue turnover are expressed in a subepidermal layer of nonneoblast cells. These subepidermal cells coexpress many PCGs. We propose that these subepidermal cells provide a system of body coordinates and positional information for regeneration, and identify them to be muscle cells of the planarian body wall. Almost all planarian muscle cells express PCGs, suggesting a dual function: contraction and control of patterning. PCG expression is dynamic in muscle cells after injury, even in the absence of neoblasts, suggesting that muscle is instructive for regeneration. We conclude that planarian regeneration involves two highly flexible systems: pluripotent neoblasts that can generate any new cell type and muscle cells that provide positional instructions for the regeneration of any body region.


Prevalence of ras gene mutations in human colorectal cancers.
A combination of DNA hybridization analyses and tissue sectioning techniques demonstrate that ras gene mutations occur in over a third of human colorectal cancers, that most of the mutations are at codon 12 of the c-Ki-ras gene and that the mutations usually precede the development of malignancy.


Effect of deleterious mutation-accumulation on the fitness of RNA bacteriophage MS2.
RNA viruses show the highest mutation rate in nature. It has been extensively demonstrated that, in the absence of purifying selection, RNA viruses accumulate deleterious mutations at a high rate. However, the parameters describing this accumulation are, in general, poorly understood. The present study reports evidences for fitness declines by the accumulation of deleterious mutations in the bacteriophage MS2. We estimated the rate of fitness decline to be as high as 16% per bottleneck transfer. In addition, our results agree with an additive model of fitness effects.


Acute diesel fuel poisoning in goats.
The clinical, haematological and pathological features of an outbreak of diesel fuel poisoning in a group of goats are described. The major clinical signs were dullness, pneumonia and nervous signs.


[Cancer of the breast. I. Epidemiology and risk factors (our experience)].
Data concerning different risk factors for breast cancer based upon the results obtained in a study of 461 women are reported. Comparing this experience with other Italian and international series, it is concluded that the most reliable risk-index for breast cancer is the age of the woman, while less incisive, though prominent, are family history, immunodeficiency, hormonal metabolism and other environmental factors.


Polymorphic epithelial mucin from the sera of advanced breast cancer patients--isolation and partial characterisation.
The anti-breast carcinoma monoclonal antibody (MAb), NCRC-11 defines a polymorphic epithelial mucin (PEM) which is elevated in the circulation of advanced breast carcinoma patients. Here we describe the purification and partial characterisation of this component from patients' sera and its use in the production of a second generation MAb, C568 (IgM). Pooled sera was fractionated by immunoaffinity and size-exclusion chromatography and the purity of preparations assessed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Serum-derived PEM shows a similar pattern of electrophoretic mobility to PEM isolated from primary breast tumour tissue and migrates as several bands in 4% SDS polyacrylamide gels (Mr greater than 400,000). The epitope expression of PEMs isolated from either source is also similar, with both bearing topographically distinct determinants for several anti-mucin MAbs. The immunoreactivities of antibodies C568 and NCRC-11 were unaffected by boiling, reduction and alkylation, or by enzyme desialylation of PEM. Periodate oxidation and proteolytic digestion have suggested that the antigenic determinant for C568 is carbohydrate in nature whilst that of NCRC-11 is peptidic. In accord with the mucinous nature of the molecule, serum-derived PEM is susceptible to reductive beta-elimination, elutes in the void volume of a Sepharose CL-4B column and has a buoyant density of 1.45 g ml-1.


Control of astigmatism after surgery and trauma: a new technique.
Five patients were subjected to a new technique designed to correct high astigmatism not responding to suture removal or adjustment. The method is described and its use illustrated in five case histories. Four of the five cases were successfully treated. The reasons for the one failure are discussed. All procedures were uncomplicated. The technique is simple, safe, and reversible.


Transversus abdominis plane block provides effective and safe anesthesia in the cesarean section for an amyotrophic lateral sclerosis parturient: A case report.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with the fatal course of muscle weakness. The published experience of anesthesia management in the cesarean section with ALS parturient is scant. A 34-year-old woman was admitted to our center complaining of obvious dysphagia together with atrophy and weakness of quadriceps at 24 weeks of her pregnancy. Cesarean was planned at 36 weeks' gestation due to the rapid deterioration of the mother. The results of neurological examination, electromyography and spinal magnetic resonance imaging suggested ALS according to the EI Escorial World Federation of Neurology criteria. Ultrasound-guided transversus abdominis plane block with 0.6 minimum alveolar concentration sevoflurane was used in this ALS parturient during her cesarean section procedure. This anesthesia strategy successfully met the demands of the surgery, helped avoid prolonged ventilation and prevent maternal respiratory complications. Transversus abdominis plane block with subanesthetic concentrations of sevoflurane can provide effective and safe anesthesia in the cesarean section for a patient with ALS.


AcMNPV ac143 (odv-e18) is essential for mediating budded virus production and is the 30th baculovirus core gene.
Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac143 (odv-e18) is a late gene that encodes for a predicted 9.6 kDa structural protein that locates to the occlusion derived viral envelope and viral induced intranuclear microvesicles [Braunagel, S.C., He, H., Ramamurthy, P., and Summers, M.D. (1996). Transcription, translation, and cellular localization of three Autographa californica nuclear polyhedrosis virus structural proteins: ODV-E18, ODV-E35, and ODV-EC27. Virology 222, 100-114.]. In this study we demonstrate that ac143 is actually a previously unrecognized core gene and that it is essential for mediating budded virus production. To examine the role of ac143 in the baculovirus life cycle, we used the AcMNPV bacmid system to generate an ac143 knockout (KO) virus (AcBAC(ac142)(REP-ac143KO)). Fluorescence and light microscopy showed that infection by AcBAC(ac142)(REP-ac143KO) is limited to a single cell and titration assays confirmed that AcBAC(ac142)(REP-ac143KO) was unable to produce budded virus (BV). Progression to very late phases of the viral infection was evidenced by the development of occlusion bodies in the nuclei of transfected cells. This correlated with the fact that viral DNA replication was unaffected in AcBAC(ac142)(REP-ac143KO) transfected cells. The entire ac143 promoter, which includes three late promoter motifs, is contained within the ac142 open reading frame. Different deletion mutants of this region showed that the integrity of the ac142-ac143 core gene cluster was required for the bacmids to display wild-type patterns of viral replication, BV production and RNA transcription.


Usefulness of TC-99M GSA liver scintigraphy for the assessment of recurrent hepatitis C after living-donor liver transplantation: a case report.
Recurrence of hepatitis C after living-donor liver transplantation was investigated using technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin (Tc-99m-GSA) liver scintigraphy. A 55-year-old woman with cirrhosis due to chronic hepatitis C virus (HCV) infection underwent liver transplantation with a graft from her husband. Scintigraphy was used to determine the hepatic uptake ratio of the tracer corrected for disappearance from the blood, as well as the maximal removal rate of the tracer by hepatocytes, as parameters of hepatic functional reserve. Conventional liver function parameters and the graft volume (computed tomography) were almost unchanged up to 18 months after transplantation. Serum HCV RNA was elevated from 3 months after transplantation, and was twofold higher at 12 months compared with 6 months. At 18 months postoperatively, liver biopsy showed an increase of histologic activity, and there was also evidence of recurrent hepatitis C. The corrected hepatic uptake ratio and maximal removal rate were decreased at 3 months postoperatively, and thereafter remained low. The decrease of scintigraphic parameters at 3 months after transplantation suggested recurrent hepatitis C affecting the graft. Tc-99m-GSA liver scintigraphy is a useful noninvasive method for evaluating graft functional reserve.


Ultrasensitive detection of inhaled organic aerosol particles by accelerator mass spectrometry.
Accelerator mass spectrometry (AMS) was shown to be applicable for studying the penetration of organic aerosols, inhaled by laboratory mice at ultra-low concentration ca. 10(3) cm(-3). We synthesized polystyrene (PS) beads, composed of radiocarbon-labeled styrene, for testing them as model organic aerosols. As a source of radiocarbon we used methyl alcohol with radioactivity. Radiolabeled polystyrene beads were obtained by emulsifier-free emulsion polymerization of synthesized (14)C-styrene initiated by K2S2O8 in aqueous media. Aerosol particles were produced by pneumatic spraying of diluted (14)C-PS latex. Mice inhaled (14)C-PS aerosol consisting of the mix of 10(3) 225-nm particles per 1 cm(3) and 5·10(3) 25-nm particles per 1 cm(3) for 30 min every day during five days. Several millions of 225-nm particles deposited in the lungs and slowly excreted from them during two weeks of postexposure. Penetration of particles matter was also observed for liver, kidneys and brain, but not for a heart.


Correlation Between High-sensitivity C-reactive Protein and Reactive Oxygen Metabolites During A One-year Period Among Asymptomatic Subjects.
Inflammation and oxidative stress are associated with human health and the disease status. The present study aimed to investigate the longitudinal correlation between the diacron reactive oxygen metabolites (d-ROMs) level, as an oxidative stress-related marker, and high-sensitivity C-reactive protein (hsCRP), as an inflammatory marker, during a one-year period among asymptomatic subjects. The data, including anthropometric and biochemical markers, were collected at baseline and after the one-year period from 71 participants (male/female = 41/30, mean age 50 years). The correlation between the changes of the d-ROMs and hsCRP levels during the study period was examined. A simple correlation analysis showed a significant and positive correlation to exist between the changes of the d-ROMs and hsCRP levels (r = 0.40, P < 0.01). This significant correlation remained independent in a multiple linear regression analysis adjusted for confounding factors. The present findings suggest that the relationship between the d-ROMs and hsCRP levels could be prospectively followed, and that monitoring both markers may help to better understand the cooperation of inflammation and oxidative stress in association with health and disease. Further studies are necessary to clarify the biological mechanism(s) responsible for the observed relationship. Oxidative stress; Oxygen reactive species; Inflammation; CRP.


Increase in oxidative stress levels following welding fume inhalation: a controlled human exposure study.
Tungsten inert gas (TIG) welding represents one of the most widely used metal joining processes in industry. It has been shown to generate a large majority of particles at the nanoscale and to have low mass emission rates when compared to other types of welding. Despite evidence that TIG fume particles may produce reactive oxygen species (ROS), limited data is available for the time course changes of particle-associated oxidative stress in exposed TIG welders. Twenty non-smoking male welding apprentices were exposed to TIG welding fumes for 60 min under controlled, well-ventilated settings. Exhaled breathe condensate (EBC), blood and urine were collected before exposure, immediately after exposure, 1 h and 3 h post exposure. Volunteers participated in a control day to account for oxidative stress fluctuations due to circadian rhythm. Biological liquids were assessed for total reducing capacity, hydrogen peroxide (H2O2), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations at each time point. A linear mixed model was used to assess within day and between day differences. Significant increases in the measured biomarkers were found at 3 h post exposure. At 3 h post exposure, we found a 24 % increase in plasma-H2O2 concentrations ([95%CI: 4 % to 46 %], p = 0.01); a 91 % increase in urinary-H2O2 ([2 % to 258 %], p = 0.04); a 14 % increase in plasma-8-OHdG ([0 % to 31 %], p = 0.049); and a 45 % increase in urinary-8-OHdG ([3 % to 105 %], p = 0.03). Doubling particle number concentration (PNC) exposure was associated with a 22 % increase of plasma-8-OHdG at 3 h post exposure (p = 0.01). A 60-min exposure to TIG welding fume in a controlled, well-ventilated setting induced acute oxidative stress at 3 h post exposure in healthy, non-smoking apprentice welders not chronically exposed to welding fumes. As mass concentration of TIG welding fume particles is very low when compared to other types of welding, it is recommended that additional exposure metrics such as PNC are considered for occupational risk assessments. Our findings highlight the importance of increasing awareness of TIG welding fume toxicity, especially given the realities of welding workplaces that may lack ventilation; and beliefs among interviewed welders that TIG represents a cleaner and safer welding process.


The Cleft Lip Nose: Primary and Secondary Treatment.
This article presents an overview of the cleft lip nasal deformity and its treatment. The complex pathologic changes to normal nasal anatomy are described, and treatment strategies for both unilateral and bilateral cleft lip patients are presented. The surgical technique for management of the cleft lip nasal deformity is discussed as it pertains to both primary and secondary correction.


[Polar constituents of the ascidia Botryllus schlosseri].
Eighteen compounds were identified by GC-MS of their trimethylsilyl derivatives in n-butanolic extract from the biomass of Botryllus schlosseri. Three of them, 5-oxoproline, 5-hydroxyhydantoin, and kinurenic acid, were found in marine invertebrates for the first time. In addition to cellulose, the biomass was also shown to contain complex water-soluble sulfated polysaccharides. These were extracted and fractionated, and sulfate content and monosaccharide composition were determined in the fractions; fucose, xylose, galactose, mannose, glucose, glucosamine, galactosamine, and uronic acids were found. Unlike several other tunicate species, Botryllus schlosseri does not seem to contain any simple galactan sulfate.


Aerobic biodegradation of high explosive hexahydro-1,3,5- trinitro-1,3,5-triazine by Janibacter cremeus isolated from contaminated soil.
To evaluate the ability of Janibacter cremeus a soil bacterium isolated from explosive contaminated site in degradation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and to study enzyme responsible for degradation. The isolate exhibited 88% degradation of RDX in 30 days of incubation. The biodegradation process followed the first order kinetics. The half- life of RDX was calculated to be 11.088 days. The RDX degradation process was complemented by concomitant release of nitrite ions with 0.78 mol of nitrite released per mole of RDX. The metabolites; Trinitroso- RDX, diamino-RDX, trimino-RDX, bis- (hydroxymethyl) nitramine and methylenedintramine derivative, viz, methylene- N- (hydroxy- methyl)- hydroxylamine- N-(hydroxymethyl) nitroamine corresponding to the molecular weights 174, 162, 132, 122 and 167 Da respectively were also detected. Nitroreductase enzyme was found to be responsible for RDX degradation. J. cremeus could degrade RDX as sole source of nitrogen, via three different pathways wherein, Nitroreductase enzyme was found to play a major role. The efficient degradation of RDX makes J. cremeus suitable in treatment of contaminated water and soil at field scale levels.


[Follow-up care at home after outpatient surgery].
Private nurses have an important role to play in the healthcare system, notably within the framework of outpatient surgery. They are often underestimated, but they are on the front lines when it comes to informing patients, reassuring them and caring for them. They must therefore master the processes of outpatient surgery and those of enhanced recovery after surgery. Their skills need to be upgraded.


A study of gonadal organogenesis, and the factors influencing regeneration following surgical castration in Deroceras reticulatum (Pulmonata:Limacidae).
At hatching, the hermaphrodite duct of Deroceras reticulatum consists of a single cell type designated the Gonadal Stem Cell (GSC). Proliferation of the GSC leads to the formation of numerous ductules each of which forms one of the acini of the gonad. The germinal and supporting cells are derived entirely from the GSC. The germ cells differentiate first, followed by the Sertoli and follicle cells. At the early sperm stage of gonadal development the hermaphrodite duct differentiates to function as a seminal vesicle. Once the GSC are committed to this change they lose their regenerative ability. The only remaining GSC are the cells of the acinar epithelium, and these retain their germinal potential until the death of the animal. Regeneration will occur from the hermaphrodite duct provided it is in the immature state, i.e., composed of GSC, and is exposed to the hormonal conditions of a young animal. Nervous connections and the presence of an artery are not necessary for this regeneration. The presence of a functional gonad does not inhibit regeneration.


An in vitro evaluation of prostaglandin E1 and I2 on hypothermic injury to immature myocytes.
The purpose of this study was to evaluate the functional and biochemical effects of Prostaglandin E1 (PGE1) and prostaglandin I2 (PGI2) on cardiac myocytes incubated under hypothermic conditions. Cardiac myocytes were isolated from neonatal rat ventricles and cultured for 4 days with MCDB 107 medium. Following this, 12.5 x 10(5) myocytes/flask were incubated at 4 degrees C for 24 h in media with PGE1, at concentrations of 0 M (group E0), 10(-9) M (group E1), 10(-8) M (group E2), 10(-7) M (group E3), or 10(-6) M (group E4); or with PGI2 at concentrations of 0 M PGI (group I0), 10(-9) M (group I1), 10(-8) M (group 12), 10(-7) M (group I3), or 10(-6) M (group I4). After hypothermic incubation, creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) were measured, and the myocytes were then cultured for 24 h at 37 degrees C to evaluate the recovery of the myocyte beating rate. Of the PGI2 groups, only group I2 recovered significantly more than the control group (group I0), at 47.9 +/- 28.5% (mean +/- SD) of the control, being the beating rate prior to hypothermic incubation, whereas it was 18.1 +/- 9.7% in group I0 (P < 0.025); however, there were no significant differences among the PGE1 groups. Moreover, the release of CPK and LDH was significantly suppressed in group 12 compared to the control, being 57.7 +/- 27.6 mIU/flask (P < 0.05) and 275.1 +/- 83.0 mIU/flask (P < 0.025), respectively, in group I2, and 96.8 +/- 38.3 mIU/flask and 439.6 +/- 147.1 mIU/flask in group I0. Again, no significant differences were observed among the PGE1 groups. In conclusion, PGI2 was found to have a direct cytoprotective effect on immature myocytes which suggests that PGI2 may promote cardiac preservation in the neonatal period.


The 675-nm wavelength for treating facial melasma.
Melasma is an acquired skin problem. It characterises sun-exposed areas, particularly on the face, with irregular borders and bilateral distribution. With this study, we want to strengthen the scientific literature regarding the use of a 675-nm laser device for the treatment of women and men with facial melasma pigmentary and vascular symptoms. Eighteen patients were treated for facial melasma. A total of three sessions at 30-day intervals were performed with a 675-nm laser device. A five-point Global Aesthetic Improvement Scale was used to separately assess the improvement of the patient's skin 3 months after the last treatment (T1) compared to baseline (T0). The pain during treatment was measured using a Visual Analog Scale of 10 points. The non-ablative laser system used emits red light with a wavelength of 675 nm through a 13 × 13 mm scanning system. At T1 , a consistent improvement in the pigmentary and vascular components was visible. This is always combined with a considerable reduction in vascular expression. Our research shows that individuals with Fitzpatrick phototypes II to III can treat facial melasma with the 675-nm laser source system without risk. Due to its interaction with melanin, collagen and haemoglobin chromophores, as well as its excellent capacity to penetrate tissues with less heating, this system is promising in the treatment of pigmentary and vascular illnesses such as melasma. The great success of the technology we used came from the reduced levels of inflammation produced after the treatments and the low energy level implied.


Use of DNA hybridization to detect vaginal pathogens associated with bacterial vaginosis among asymptomatic pregnant women.
The purpose of this study was to determine whether microbial DNA hybridization is a useful method to study bacterial vaginosis in asymptomatic pregnant women. Vaginal specimens were collected at <26 weeks' gestation from 230 women, and analyzed for bacterial vaginosis by both Gram stain using Nugent criteria and DNA hybridization for Gardnerella vaginalis, Prevotella bivia, Bacteroides ureolyticus, and Mobiluncus curtisii. Results were analyzed using McNemar's paired test and chi-square test for trend, with significance set at P < .05. By Gram stain, 60 (26.1%) of 230 were positive for bacterial vaginosis, and 134 (58.3%) were negative. By DNA hybridization, 99 (43%) were positive for at least 1 pathogen, and DNA results were significantly associated with Gram-stain results (P < .01). As the Nugent score progressed from normal to abnormal flora, the proportion with >1 pathogen detected by DNA hybridization increased significantly (P < .001). DNA hybridization may be a useful method to study shifts in vaginal flora during pregnancy.


OsFAR1 is involved in primary fatty alcohol biosynthesis and promotes drought tolerance in rice.
OsFAR1 encodes a fatty acyl-CoA reductase involved in biosynthesis of primary alcohols and plays an important role in drought stress response in rice. Cuticular waxes cover the outermost surface of terrestrial plants and contribute to inhibiting nonstomatal water loss and improving plant drought resistance. Primary alcohols are the most abundant components in the leaf cuticular waxes of rice (Oryza sativa), but the biosynthesis and regulation of primary alcohol remain largely unknown in rice. Here, we identified and characterized an OsFAR1 gene belonging to the fatty acyl-CoA reductases (FARs) via a homology-based approach in rice. OsFAR1 was activated by abiotic stresses and abscisic acid, resulting in increased production of primary alcohol in rice. Heterologous expression of OsFAR1 enhanced the amounts of C22:0 and C24:0 primary alcohols in yeast (Saccharomyces cerevisiae) and C24:0 to C32:0 primary alcohols in Arabidopsis. Similarly, OsFAR1 overexpression significantly increased the content of C24:0 to C30:0 primary alcohols on rice leaves. Finally, OsFAR1 overexpression lines exhibited reduced cuticle permeability and enhanced drought tolerance in rice and Arabidopsis. Taken together, our results demonstrate that OsFAR1 is involved in rice primary alcohol biosynthesis and plays an important role in responding to drought and other environmental stresses.


Carnosic acid, a phenolic diterpene from rosemary, prevents UV-induced expression of matrix metalloproteinases in human skin fibroblasts and keratinocytes.
Exposure of the skin to ultraviolet (UV) irradiation induces photoageing through the up-regulation of matrix metalloproteinases (MMPs) and subsequent breakdown of extracellular matrices. Reactive oxygen species (ROS) and epidermal growth factor receptor (EGFR) activation play central roles in UV-induced MMP expression through initiating extracellular signal-regulated kinase (ERK)-mediated AP-1 signalling. We aimed to explore the effects of carnosic acid (CA), a phenolic diterpene from rosemary, on UV-induced MMP expression in human skin cells. Molecular mechanism underlying the effects of CA was also examined in the aspect of MMP expression, ERK/AP-1 pathway, ROS generation and EGFR activation. Human dermal fibroblast cell line (Hs68), primary normal human dermal fibroblasts (HDFs) and normal human epidermal keratinocytes (HEKs) were employed, and antiphotoageing effects of CA were assessed by Western blotting, quantitative real-time PCR and enzyme assays. CA significantly inhibited UVA- and UVB-induced expression of MMP-1, MMP-3 and MMP-9 in a concentration-dependent manner in Hs68 cells. UVB-induced ERK activation and the formation of transcription factor, AP-1, were significantly suppressed by CA. Among the upstream events of MMP expression, UVB-induced ROS generation was attenuated by CA, while EGFR activation was not affected. Confirming the antiphotoageing effects of CA through the suppression of UV-induced ROS generation, UVB-enhanced GADD45 expression, a marker for oxidative DNA damages was significantly reduced by CA. Inhibitory effects of CA on UVB-induced MMP expression could be also seen in HDFs and HEKs. Collectively, our study demonstrates that CA inhibits the UV-enhanced MMPs in human skin cells through the inhibition of ROS and the suppression of ERK/AP-1 activation.


Prostaglandin D2 Modulates Neuronal Excitation of the Trigeminal Ganglion to Augment Allergic Rhinitis in Guinea Pigs.
Prostaglandin D2(PGD2) is involved in the pathogenesis of allergic rhinitis. However, the sensory nervous system-mediated contributions of PGD2to the symptoms of allergic rhinitis remain unclear. We investigated the involvement of PGD2in these symptoms and in neuronal excitation by in vivo and ex vivo experiments. In an ovalbumin-induced model of allergic rhinitis in guinea pigs, the number of sneezing, nasal rubbing, and nasal secretion events were assessed after the nasal cavity instillation of PGD2, histamine, or a combination of PGD2and histamine. In situ hybridization for PGD2receptor 1 (DP1) mRNA transcripts and immunohistochemical analysis of histamine H1receptor protein expression in guinea pig trigeminal ganglion (TRG) were performed. The effects of DP1receptor activation on the excitability of TRG neurons to electrical and histamine stimuli were assessed using whole-cell patch-clamp recordings. Histamine induced more sneezing, nasal rubbing, and nasal secretion events than PGD2 PGD2augmented histamine-induced responses, whereas pretreatment with a DP1receptor-selective antagonist completely suppressed PGD2-induced augmentation. DP1receptor mRNA transcripts and H1receptor protein expression could be detected in TRG neurons. Moreover, a DP1receptor agonist caused significant increases in the number of histamine-induced action potentials and depolarization, and reduced the current threshold in small-diameter neurons. Our findings show that PGD2-DP1receptor signaling augments the symptoms of allergic rhinitis via the sensory nervous system by modulating nasal neuronal activation to various stimuli, such as histamine. These findings suggest that DP1receptor antagonist has therapeutic potential for the treatment of allergic rhinitis.


Influence of ionic strength, EDTA concentration, endogenous C1q and polyanions on the 125I-C1q-binding test.
Several parameters of the 125I-C1q-binding test were investigated: ionic strength, pH, concentration of EDTA, influence of serum C1q and the possibility of interference by polyanions. Lowering the ionic strength of the borate buffer resulted in increased precipitation of 125I-C1q in normal human serum. This increase was dependent on the presence of serum proteins, probably immunoglobulins. When the concentration of the EDTA was decreased, increased precipitation of 125I-C1q in normal human serum was also observed. This was prevented by adding NaCl to the EDTA solution. However at very low concentrations of EDTA (too low to chelate all calcium ions in the serum), increased precipitation of 125I-C1q in normal human serum was observed even in the presence of added NaCl. Addition of purified C1q to sera from patients with very low C1q levels had varying effects on the results of the C1q-binding test: (a) it decreased the C1q-binding activity of some sera, probably by competition with 125I-C1q for binding sites on the immune complexes; (b) it increased the C1q-binding activity of other sera, probably by enhancing the precipitation of immune complexes as a consequence of the cross-linking effect of C1q; or (c) it had no influence, possibly due to the opposite effects of (a) and (b). The addition of dextran sulphate resulted in a dose-dependent increase in the 125I-C1q-binding activity of normal human serum. This effect was dependent on the interaction of dextran sulphate with either C1q or low-density lipoproteins and was prevented by addition of polybrene to the assay. However, addition of polybrene to sera with a high C1q-binding activity scarcely influenced binding activity.


Downregulation of striatal dopamine D2 receptors in advanced Parkinson's disease contributes to the development of motor fluctuation.
The purpose of this study was to evaluate the contribution of the postsynaptic mechanism to the development of motor fluctuation in advanced Parkinson's disease (PD). We used 123I-iodobenzamide single-photon emission computed tomography to measure the striatal dopamine D2 receptor densities in early levodopa-naïve PD, chronic PD with stable levodopa response, and advanced PD with fluctuating levodopa response. The basal ganglia/frontal cortex ratios at both hemispheres were calculated and averaged. PD patients with fluctuating levodopa response showed a significant decrease in striatal dopamine D2 receptor densities compared to those with early (1.57+/- 0.20 vs. 1.77 +/- 0.12, p = 0.009) or chronic stable PD (1.57 +/- 0.20 vs. 1.77 +/- 0.10, p = 0.024). We conclude that the decreased D2 receptor densities in advanced PD reduced the 'safety factor' for synaptic transmission and contributed to the development of motor fluctuation.


Dendritic cells development into osteoclast-type APCs by 4T1 breast tumor T cells milieu boost bone consumption.
Bone metastases occur in 70% of patients with advanced breast cancer, causing severe morbidity and increased mortality due to osteolytic lesions driven by osteoclasts (OCs) inside the bone marrow (BM) microenvironment. A reciprocal vicious cycle between bone remodeling system and the tumor itself is established by the release of growth factors stored in the mineralized matrix, which in turn feed the tumor, changing tumor behavior and growth. However, BM is not a passive host microenvironment for circulating tumor cells, but instead can be actively modified by the primary tumor before metastatic spread occurs. Indeed, we have shown that T cells specific for the 4T1 mammary carcinoma cell line, are characteristically RANKL+ IL-17F+ CD4+ T cells. Those cells arrive in the BM before metastatic cells and set the pre-metastatic niche. In the absence of T cell derived RANKL, there is no pre-metastatic osteolytic disease and bone metastases do not take place. Recently, dendritic cells (DCs), the main T cell partner at the beginning of the immune response, came into the spotlight as a potential source of OCs progenitors under inflammatory conditions. Regarding bone metastasis, nothing is currently known about DCs plasticity or even its partnership with tumor induced T cells for BM pre-metastatic niche formation. Here, we show that splenic CD11c+ DCs stimulated with 4T1 conditioned media (CM) efficiently differentiated into mature and activated multinucleated giant cells (DC-OC) expressing TRAP and IL-23 cytokine. More important, 4T1 CM derived DC-OCs build a positive loop which amplifies the osteolytic phenomena by maintaining the RANKL+ Th17 T cells and by its own osteoclastic activity. In conclusion, our results indicate that differentiation of OCs from DCs may be achievable in the bone pre osteolytic disease context representing an alternative OC differentiation pathway. Besides being induced by high levels of T cells pro osteoclastogenic cytokines, especially by RANKL, DC-OC keep a positive feedback loop towards osteolysis, maintaining the pro-osteoclastogenic T cell phenotype in the BM.


Decision-making at the border of viability: determining the best interests of extremely preterm infants.
This paper proposes and employs a framework for determining whether life-saving treatment at birth is in the best interests of extremely preterm infants, given uncertainty about the outcome of such a choice. It argues that given relevant data and plausible assumptions about the well-being of babies with various outcomes, it is typically in the best interests of even the youngest preterm infants-those born at 22 weeks gestational age-to receive life-saving treatment at birth.


Structural insight into the activation of an Arabidopsis organellar C-to-U RNA editing enzyme by active site complementation.
RNA-binding pentatricopeptide repeat (PPR) proteins catalyze hundreds of cytidine to uridine RNA editing events in plant organelles; these editing events are essential for proper gene expression. More than half of the PPR-type RNA editing factors, however, lack the DYW cytidine deaminase domain. Genetic analyses have suggested that their cytidine deaminase activity arises by association with a family of DYW1-like proteins that contain an N-terminally truncated DYW domain, but their molecular mechanism has been unclear. Here, we report the crystal structure of the Arabidopsis thaliana DYW1 deaminase domain at 1.8 Å resolution. DYW1 has a cytidine deaminase fold lacking the PG box. The internal insertion within the deaminase fold shows an α-helical fold instead of the β-finger reported for the gating domain of the A. thaliana ORGANELLE TRANSCRIPT PROCESSING 86. The substrate-binding pocket is incompletely formed and appears to be complemented in the complex by the E2 domain and the PG box of the interacting PPR protein. In vivo RNA editing assays corroborate the activation model for DYW1 deaminase. Our study demonstrates the common activation mechanism of the DYW1-like proteins by molecular complementation of the DYW domain and reconstitution of the substrate-binding pocket.


Biochemical characterization and purification of human B cell stimulatory factor (BSF).
B cell stimulatory factor (BSF) activity was generated over a period of five days by phytohemagglutinin-stimulated E rosette-positive peripheral blood lymphocytes. This activity was subjected to a multistep purification procedure including ammonium sulfate precipitation, anion-exchange chromatography, gel filtration, procion red-agarose chromatography and reverse phase high performance liquid chromatography (RP-HPLC). The last purification step dissected BSF activity into two active fractions, one corresponded to the interleukin 2 (IL 2) activity whereas the other active fraction was free of IL 2 activity. Preparative isoelectric focusing analysis defined isoelectric points of pH 7.2 for both BSF and IL 2. Molecular weight analysis of BSF was carried out by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. BSF activity was eluted from gel strips corresponding to a molecular mass of 16 and 17 kDa. The 16-kDa fraction was free of IL 2 activity whereas the 17-kDa fraction overlapped with IL 2. Since recombinant IL 2 was capable of exhibiting significant BSF activity in anti-IgM or Staphylococcus aureus Cowan strain I-dependent assay systems, it cannot be excluded that IL 2 itself is a BSF. Nevertheless these studies demonstrate the existence of a BSF free of IL 2 activity.


[Tours experience of endovascular treatment in superior vena cava syndrome].
Superior vena cava syndrome is a clinical entity including symptoms arising from an obstruction of return flow in the superior vena cava. It can be life threatening. In the context of lung cancer, by far the most prominent etiology (nine of ten cases in our series), the condition is particularly serious, with only 20% survival at one year. Medical treatment may be insufficient, requiring surgical salvage. Palliative procedures are rapidly effective and well tolerated. We perform a first intention transluminal angioplasty under local anesthesia via the right femoral vein. This ultrasound-guided procedure enables insertion of a non-coated nitinol stent. The success rate in our hands has been 90%. Clinical improvement is constant and immediate with long-term efficacy. The early and late post-operative period is uneventful.


Accurate determination of metabolic rates from dynamic positron emission tomography data with very-low temporal resolution.
The graphical approach is widely used for the pixelwise determination of local metabolic rate of glucose from dynamic positron emission tomography (PET) data. In its conventional implementation, measured integrals over time frames are used to approximate instantaneous tracer concentrations at midframe times ("midframe approach"). This is justified in case of high temporal resolution of the PET measurement; that is, if scan protocols with a large number of short frames are used. This requires fast data handling and large amounts of memory. Cardiac gating and three-dimensional (3D) acquisition of dynamic studies is hardly possible with this approach. Therefore, a new variant of the graphical method is proposed which can be used with a very low number of rather long frames. An operational equation of the graphical method was derived which uses measured time integrals only and, thus, avoids the systematic errors of the midframe approximation. This "integral approach" was evaluated in computer simulations based on experimental data. The integral approach enables the use of protocols with 3 frames only without compromising accuracy of the derived metabolic rates whereas the midframe approach leads to bias of about 10% to 20% for these protocols. Furthermore, test-retest stability can significantly be improved when using the integral approach. The integral approach to the graphical evaluation of dynamic PET data yields accurate and precise results using scan protocols with down to only 3 frames. This can be relevant to gating and/or 3D acquisition of dynamic studies. The integral approach is applied most naturally whenever the input function is derived from the dynamic PET data.


TP receptor-mediated release of eosinophil chemotactic activity from human bronchial smooth muscle cells.
There are reports indicating that thromboxane A(2) receptors (TP receptors) may stimulate the eosinophil accumulation in the lower airways of asthmatics, however, the mechanisms behind such an effect remain unknown. We quantified the synthesis of eosinophil chemotactic activity and eosinophilic CC chemokines, including CCL5, CCL7, CCL8, CCL11, CCL13, CCL24, and CCL26 in primary cultures of human bronchial smooth muscle cells (BSMC) stimulated with a prostanoid TP receptor agonist, IBOP (10(-9)-10(-7) M). The activation of prostanoid TP receptors in BSMC induced the release of potent eosinophil chemoattractant(s) in the presence of interleukin (IL)-4. CCL11/eotaxin-1 was the only synthesis significantly increased by IBOP co-stimulated with IL-4, and pretreatment with an anti-CCL11 antibody abrogated the eosinophil chemotactic activity released from IBOP/IL-4-stimulated BSMC. The effect of IBOP was also completely blocked by pretreatment with a prostanoid TP receptor-specific antagonist, AA-2414. IBOP had no effect on the expression of IL-4 receptor-alpha, or on the IL-4-induced phosphorylation of STAT6 in BSMC. In conclusion, activation of prostanoid TP receptors in a Th2-dominant microenvironment might exacerbate the eosinophilic inflammation of the airways by synthesis and release of CCL11 from BSMC.


Challenges in teaching systematic reviews to non-clinicians.
Systematic reviews are regarded as the cornerstone of evidence-based decision making across many disciplines. The teaching of systematic review methods is thus very important, yet it is a field that still remains unexplored. In this paper, we will outline an approach for teaching non-clinicians about systematic reviews at the University of Cologne. Our aim was to cast some light on the challenges involved and to stimulate discussion and discourse on this topic. Out of a total of twelve weeks of teaching (1.5hours per week), nine of them included hands-on exercises that cover all the steps involved in a systematic review, from defining a specific review question up to conducting and interpreting meta-analyses. The course was based on the Cochrane Handbook for Systematic Reviews of Interventions that provide specific guidance for the development and assessment of systematic reviews. A well-reported, well-conducted systematic review was used as a working example throughout the course. The course was taught by an experienced systematic reviewer without input from additional experts such as information specialists or biometricians. To improve the learning success, four fields of challenge were identified: the selection of appropriate topics for the course assignment, the selection of an appropriate guiding review, specific requirements related for the lecturer, and the integration of methodological progress.


Finger-pressing: a simple and efficient way to stop chyle leak post neck dissection.
Postoperative chyle leak (CL) is a rare but severe complication after neck dissection. Conservative first-line treatments, such as total parenteral nutrition (TPN), octreotide and pressure dressing, can significantly prolong the hospital stay. Efficient and well-tolerated conservative treatment options are still lacking. We have developed a new maneuver to treat CL called "finger-pressing." A thumb is pressed against the point of leakage between the two muscle heads of the sternocleidomastoid. Finger-pressing continues for about 24 h until CL stops. We used this maneuver to treat six CL patients. Drainage output and duration of hospital stay were compared with another six CL patients treated using the traditional pressure dressing. The finger-pressing maneuver cured all six CL patients. Most CLs (5/6) could be controlled after about 24 h pressing. Only one high-output CL required 72 h of finger-pressing to stop the leak. All patients had their drainage tubes removed within 3 days after pressing started and all patients tolerated the treatment well. In the control group, the traditional pressure dressing time varied from 2 to 5 days, until the patient was no longer able to cooperate. Three patients underwent a second operation that cured the CL in two cases. The average hospital stay was significantly longer than that in the finger-pressing group (20 vs 9 days, p = 0.037). Finger-pressing is an efficient and well-tolerated method for treating CL post neck dissection. This maneuver could be a useful adjuvant therapy to traditional methods in treating CL.


Randomized clinical trial of the effectiveness of emergency day surgery against standard inpatient treatment.
The aim of this study was to assess the feasibility of treating patients with minor and intermediate general surgical emergency conditions as day cases. Emergency referrals for minor and intermediate general surgical conditions were assessed by a surgeon. Those fitting day-case criteria and requiring operation under general anaesthesia were randomized to receive standard inpatient care or day surgery. Patients in the latter group were booked on to day-case lists or gaps on inpatient elective lists for surgery within 48 h. The process was coordinated by an experienced theatre sister. One hundred patients were randomized. There was a reduction in the number of nights spent in hospital in the day-case group (median 0 versus 2 nights; P < 0.001). The median time from diagnosis to treatment was 1 day in both groups, although there was a small but significant delay in the day-case group (P = 0.018). There was no significant difference in postoperative outcome or patient and general practitioner satisfaction. The day-case option had no increased impact on primary care services but was associated with a significant saving of about pound sterlings 150 per patient (P < 0.001). Certain general surgical emergencies may be managed as day cases with cost saving but without detriment to patient care.


Caspase-3 activation as a bifurcation point between plasticity and cell death.
Death-mediating proteases such as caspases and caspase-3 in particular, have been implicated in neurodegenerative processes, aging and Alzheimer's disease. However, emerging evidence suggests that in addition to their classical role in cell death, caspases play a key role in modulating synaptic function. It is remarkable that active caspases-3, which can trigger widespread damage and degeneration, aggregates in structures as delicate as synapses and persists in neurons without causing acute cell death. Here, we evaluate this dichotomy, and discuss the hypothesis that caspase-3 may be a bifurcation point in cellular signaling, able to orient the neuronal response to stress down either pathological/apoptotic pathways or towards physiological cellular remodeling. We propose that temporal, spatial and other regulators of caspase activity are key determinants of the ultimate effect of caspase-3 activation in neurons. This concept has implications for differential roles of caspase-3 activation across the lifespan. Specifically, we propose that limited caspase-3 activation is critical for synaptic function in the healthy adult brain while chronic activation is involved in degenerative processes in the aging brain.


Excitation-induced Ca2+ dynamics in sympathetic neurons measured with conventional epifluorescence and confocal UV laser-scanning microscopes.
A depolarization-induced rise in intracellular Ca2+ in cultured bullfrog sympathetic ganglion cells depended non-linearly on Ca2+ influx and membrane depolarization, spread inwardly faster than that without Ca(2+)-induced Ca2+ release (CICR), and was blocked by dantrolene and ryanodine. Ca2+ entry and a graded activation of CICR thus induce the "Ca2+ transient."


[Monitoring novel ovarian carcinoma associated genes using cDNA expression microarray].
To explore the gene expression pattern of sample of human ovarian carcinoma. The difference in gene expression between normal and neoplastic human ovarian tissues were investigated, we described the assembly and utilization of a 512 member cDNA microarray. Thirty-seven genes expressed in ovarian cancer were screened out, 14 genes were up-regulated, 23 genes were down-regulated. cDNA microarray for analysis of gene expression pattern is an effective method to identify novel ovarian cancer associated genes.


Evaluation of in vitro antagonism and of in vivo immune modulation and protection against pathogenic experimental challenge of two probiotic strains of Bifidobacterium animalis var. lactis.
The aim of the present study was to compare the effect of intragastric administration with two strains of Bifidobacterium animalis subsp. lactis (Bifido A and Bifido B), in gnotobiotic and conventional mice, challenged with Salmonella Typhimurium. In vitro antagonism test showed that the two strains were able to produce antagonistic substances against various pathogenic microorganisms. In an ex vivo antagonism test the production of antagonistic substances was observed only against three out ten pathogens tested. Both Bifidobacterium strains were able to colonize and to maintain high population levels in the digestive tract of gnotobiotic mice. In addition, the two strains had low and limited translocation ability and did not cause any histological lesion in any of the organs analyzed. Both strains were able to reduce the fecal number of Salmonella in gnotobiotic mice challenged with the pathogen, but only Bifido B was able to confer a protection as demonstrated by a lower mortality. Higher levels of sIgA and IL-10 were observed only in Bifido B mono-associated mice when compared to germ free group. We could conclude that, among the parameters analyzed, the strain Bifido B exhibited the more desirable characteristics to be used as a probiotic.


Do number and location of plates impact infection rates after definitive fixation of high energy tibial plateau fractures?
Surgical trauma may confer additional infectious risk after operative fixation for high energy tibial plateau fractures. This study aims to determine the impact of plate number and location on infection rates after these injuries. This retrospective cohort study completed at two level one trauma centers included patients who underwent staged fixation for a tibial plateau fracture between 2015 and 2019. Plate number and location (lateral, medial, posteromedial, and anterior quadrants) used in the definitive fixation construct were collected from post-operative radiographs. Deep infection rate was primary the outcome. A total of 244 patients met inclusion criteria. The overall infection rate was 13.9% (34/244). Infection rates increased with each additional quadrant utilized (8.0% one quadrant, 13.0% two quadrants, 27.3% three quadrants, 100% four quadrants; p < 0.001), independent of plate number, fracture severity, operative time, number of incisions, external fixator pin and plate construct overlap, and days in the external fixator on multivariate analysis. Infection risk increases with each quadrant utilized in the fixation of high energy tibial plateau fractures. Providers should attempt to limit the dissection of soft tissue for hardware placement in the fixation of these injuries to limit infection risk. Level III, retrospective therapeutic study.


Opsonization requirements of Serratia marcescens.
Dextran-separated human peripheral blood leukocytes (55 vol%) from healthy adults served to delineate the opsonic requirements of various serologically defined assay strains of Serratia marcescens. 'Natural' antibodies of three commercial IgG immunoglobulin preparations (25 vol%), in the absence of complement (C), did not opsonize all 19 test strains, in particular certain strains carrying O-antigens O6 and/or O14, despite documented (ELISA technique) contents of anti-O6 and -O14 IgG antibodies. The 'natural' IgG opsonins proved O-antigen specific. Several of 13 selected assay strains of S. marcescens differed in opsonic requirements for 'classically' or 'alternatively' activated human C; opsonization was optimal with intact fresh human serum (25 vol%). All 13 tested strains activated both pathways of C. Anti-live cell rabbit immune sera (RIS) surpassed conventional anti-O and anti-H RIS (25 vol%) in terms of opsonizing activity, which proved partially heat-labile and O-antigen specific for two, but not for two other test strains. Isolated IgM immunoglobulin fractions of anti-live cell RIS either totally lacked or displayed inferior opsonizing activity in the absence of C, although O-agglutinin activity was only from 4- to 8-fold lower than that of unfractionated anti-live cell RIS. Human and rabbit 'natural' IgM antibodies opsonized moderately. Added guinea pig C (10 vol%) failed to enhance opsonizing activity of 'natural' and 'immune' rabbit IgM and 'natural' human IgG and IgM antibodies.


The free osteofasciocutaneous fibula flap: clinical applications and surgical considerations.
The aim of this study was to investigate the intraoperative findings, postoperative complications, donor site morbidity and patients' Quality of Life in order to evaluate the usefulness of the free osteofasciocutaneous fibula flap in the reconstruction or construction of a mandibula, neophallus, lower leg or forearm. 104 patients were treated with free osteofasciocutaneous fibula flaps in our clinic. 23 for mandible reconstruction, 66 for neophallus reconstruction, 9 for lower leg reconstruction and 6 for forearm reconstruction. These patients were asked to answer a questionnaire and to be present for a clinical and a radiological examination in our department. In addition, their previous records were evaluated retrospectively. The dimension of the surface of the skin island was 178.6 cm(2) (72-352 cm(2)) in average and the average length of the fibular bony part was 15.4 cm (10-23 cm). The most frequent and severe complication was skin island edge necrosis (n=7); no total flap necrosis was found. Donor-site morbidity was low, since no joint instability could be reported. Quality of Life was improved according to the standardised FLZ(M) questionnaire. Advantages of free osteofasciocutaneous fibula flaps were the wide cortical bone and the relative constant anatomy, the long pedicle, flat, uniform and sufficient large and pliable skin island, as well as the good blood circulation also by massive modelling of the skin and bone part. The skin island could be harvested large enough in order to reconstruct extended soft-tissue defects in the face and the extremities as well as to construct neophallus in its normal size without any restrictions. The lower leg donor-site morbidity was moderate and can be readily covered with a sock in patients' everyday life common activities. Finally, in our hands, the utilisation of the free osteofasciocutaneous fibula flap is the best possible therapy for these difficult composite reconstructions.


Hematopoietic stem cell transplantation for infantile osteopetrosis.
Infantile osteopetrosis is a lethal disorder resulting from a severe defect in the ability of osteoclasts to resorb bone. The only therapy shown to be capable of providing lasting benefit is allogeneic hematopoietic stem cell transplantation (HCT). We report the outcome of 10 patients with infantile malignant osteopetrosis treated with HCT from an HLA A, B, DRB1 matched (n=6) or A or B locus mismatched (n=4) family member or unrelated donor at the University of Minnesota between 1978 and 1997. Eight of 10 patients achieved primary engraftment; secondary graft failure was seen in two patients. Five of 10 patients survive; three with full or partial donor chimerism and two with autologous hematological recovery. Transient or partial donor chimerism can be sufficient to correct the hematological manifestations of osteopetrosis. We recommend early referral for consideration of HCT with a related or unrelated donor as neurosensory manifestations of osteopetrosis are generally not reversible. Donor engraftment may be easier to achieve early in the course of the disease.


Parasitic fungus Claviceps as a source for biotechnological production of ergot alkaloids.
Ergot alkaloids produced by the fungus Claviceps parasitizing on cereals, include three major groups: clavine alkaloids, d-lysergic acid and its derivatives and ergopeptines. These alkaloids are important substances for the pharmatech industry, where they are used for production of anti-migraine drugs, uterotonics, prolactin inhibitors, anti-Parkinson agents, etc. Production of ergot alkaloids is based either on traditional field cultivation of ergot-infected rye or on submerged cultures of the fungus in industrial fermentation plants. In 2010, the total production of these alkaloids in the world was about 20,000 kg, of which field cultivation contributed about 50%. This review covers the recent advances in understanding of the genetics and regulation of biosynthesis of ergot alkaloids, focusing on possible applications of the new knowledge to improve the production yield.


[Nursing care after thrombectomy].
Since its inception in 2015, thrombectomy has revolutionised the emergency management of ischaemic stroke with large vessel occlusion. Indeed, early endovascular extraction of the thrombus considerably improves the prognosis. Different medical teams are involved in the critically urgent management of these very fragile patients.


Subjective quality of life and depressive symptoms in women with alcoholism during detoxification treatment.
The study investigated whether subjective quality of life (SQOL) differs in alcoholic women with and without depressive symptoms being in detoxification treatment. Moreover, we tested whether depressive symptoms were correlated with other subjective evaluation criteria. SQOL and psychopathology were obtained in 70 alcoholic women during treatment. Alcoholic women with depressive symptoms showed a lower SQOL regarding several life domains, in particular their family situation, and life as a whole. Additionally, they reported more needs for support and more negative consequences of alcoholism. The findings underline the relevance of quality of life ratings in detoxification treatment and their association with depressive symptoms.


Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) as a revisional surgery.
Few studies of single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) as the revision surgery for laparoscopic adjustable gastric banding (LAGB) have been published. To explore the efficacy and safety of SADI-S as the revision surgery for LAGB. The research was completed by the University Hospital. From November 2013 to November 2015, a total of 22 weight-regain patients who previously underwent LAGB received SADI-S as the revision surgery at the People's Liberation Army General Hospital. Preoperative clinical characteristics as well as the data at 1, 3, 6, 12, 18, and 24 months after operation were collected and analyzed. The operation time of SADI-S was 105 ± 12.2 minutes, and intraoperative blood loss was 27.3 ± 5.8 mL. The percentage of excess weight loss was 20.55 ± 9.10%, 40.1 ± 6.02%, 63.52 ± 10.43%, 70.72 ± 8.54%, 78.34 ± 9.25%, and 81.57 ± 11.12% at 1, 3, 6, 12, 18 and 24 months after surgery, respectively. The 2-year complete remission rate of type 2 diabetes was 17 of 18, and the partial remission rate was 1 of 18 after operation. The glycated hemoglobin was 8.7% ± 1.1%, 7.7% ± .9%, 6.2% ± .6%, 5.7% ± .5%, 5.5% ± .6%, 6.0% ± .9%, and 5.7% ± .8% preoperatively and at 1, 3, 6, 12, 18, and 24 months after the operation, respectively. One case presented incisional hernia and was repaired. There was no conversion to laparotomy. Vitamins and trace elements were administrated long term to these patients after the operation, and no patients experienced vitamin or trace element deficiencies. SADI-S is safe and effective as a revision surgery for patients who experienced weight regain after LAGB. However, multicenter randomized controlled studies with larger sample sizes are needed to explore the long-term efficacy and safety of SADI-S.


Central retinal artery resistive index and optical coherence tomography in assessment of glaucoma progression.
To assess the relation between central retinal artery (CRA) resistive index (RI) and retinal nerve fiber thickness measured by optical coherence tomography (OCT) in assessment of disease progress in cases of open angle glaucoma. Twenty-three patients with diagnosed open angle glaucoma were included in this study. They were examined by colored duplex ultrasonography of CRA with estimation of RI of CRA and ophthalmic artery (OA) with estimation of CRA/OA RI ratio as well as OCT measurement of the average retinal nerve fiber layer (RNFL) thickness in order to assess the disease progress. There was strong inverse relation between the increased RI in CRA as well as the increased CRA/OA RI ratio and the decrease in average RNFL thickness in cases of open angle glaucoma. Assessment of CRA RI can indirectly assess the vascular changes associated with glaucoma and can assess the degree of retinal atrophy helping in evaluating prognosis thus guiding the choice of treatment.


Additive Manufacturing of a Microbial Fuel Cell--A detailed study.
In contemporary society we observe an everlasting permeation of electron devices, smartphones, portable computing tools. The tiniest living organisms on Earth could become the key to address this challenge: energy generation by bacterial processes from renewable stocks/waste through devices such as microbial fuel cells (MFCs). However, the application of this solution was limited by a moderately low efficiency. We explored the limits, if any, of additive manufacturing (AM) technology to fabricate a fully AM-based powering device, exploiting low density, open porosities able to host the microbes, systems easy to fuel continuously and to run safely. We obtained an optimal energy recovery close to 3 kWh m(-3) per day that can power sensors and low-power appliances, allowing data processing and transmission from remote/harsh environments.


Transcriptomic insights into the heat stress response of Dunaliella bardawil.
The halophilic green alga Dunaliella bardawil has been used for commercial production of natural β-carotene by large-scale outdoor cultivation, which often suffers from heat stress especially at noon in hot summers. In this study, the effects of heat stress on cell growth, pigment contents, and activities of antioxidant system in D. bardawil were studied, and RNA-seq experiment was conducted to analyze the transcriptional response to heat stress (42 °C for 2 h) in D. bardawil. High temperature (42 °C) for short time treatment (≤3 h) did not severely affect the cell growth and pigment accumulation of D. bardawil. Multiple genes encoding heat shock proteins for protein folding and antioxidant enzymes against toxic reactive oxygen species were substantially up-regulated significantly under heat stress. D. bardawil cells tended to shift from aerobic to glycolytic metabolism for energy production to increase survival chances under heat stress. Furthermore, the enrichment of ascorbate-glutathione cycle, up-regulation of genes responsible for chloroplast membranes, and changes in lipid characteristics like carbon chain length and unsaturation degree could play a vital role in achieving thermotolerance of D. bardawil. Taken together, this study improved our understanding of the molecular mechanisms of heat stress responses in D. bardawil.


Rod receptors in the retina of Tupaia belangeri.
The retina of Tupaia belangeri was studied by transmission electron microscopy. - Among a vast majority of cones a few typical rods have been found as a distinctly different class of photoreceptors. The outer segments of the rods measure 10 microns X 1.5 microns versus 6 microns X 2 microns in the cones. The repeating unit of the rod discs is 18 nm versus 22 nm in the cone discs. Rod discs tend to lose their continuity with the ciliary membrane, while cone discs do not. Rods lack the highly specialized giant mitochondria of the cone inner segment of Tupaia. The rods of Tupaia show other distinctive characters of mammalian rods as well. However, the rods of Tupaia are relatively short and do not develop a rod fiber.


Medium-term results of cryoballoon ablation of the pulmonary veins in patients with paroxysmal and persistent atrial fibrillation. First experience of a Spanish center.
Cryoballoon ablation of the pulmonary veins (CAPV) is a new technique that could have similar results to radiofrequency procedures, but with fewer complications. We analyzed the outcomes and safety of this technique in a consecutive cohort of patients with atrial fibrillation (AF). A total of 63 patients with paroxysmal (n = 40) or persistent (n = 23) AF were studied. Patient follow-up was performed at 3 months and then every 6 months with 72-h continuous electrocardiographic recordings. A total of 262 pulmonary veins were treated; 60.3 % of the cases presented normal pulmonary vein drainage with 4 pulmonary veins, and 23.8 % of the cases presented a common left-sided antrum. Complete isolation of all veins was achieved in 95.2 % of cases with 10.3 ± 2.8 (mean ± standard deviation) applications per patient. Transient right phrenic nerve injury was the most common complication (4.7 %). Median follow-up was 5.5 months. The probability of being free of recurrence at 1 and 2 years was, respectively, 86.2 and 72.2 % for paroxysmal AF and 49 and 36.4 % for persistent AF (P = 0.012). Patients with structural heart disease experienced recurrence more often than patients with a normal heart (62.5 versus 24.5 %; P = 0.03). CAPV appears to be a safe and effective procedure for the treatment of patients with AF, particularly those with paroxysmal AF and no structural heart disease.


Mothering at a Distance: what incarcerated mothers value about a parenting programme.
Children with incarcerated mothers experience adverse health, social and emotional circumstances, and are a particularly vulnerable group. Mothers in custody face significant challenges in parenting their children. The study aimed to identify participants' views on impact of a parenting support programme for incarcerated mothers in NSW Australia. The mixed-methods study examined 134 responses to open and closed questions on a questionnaire for programme participants. Participants found the programme worthwhile, engaging and relevant. It enhanced their parenting knowledge and confidence. Open-ended responses highlighted program elements which participants valued, specifically support for their parenting role in complicated circumstances, greater understanding of child development and perspectives, and practical strategies for facilitating connections with their children during their incarceration. The study informs nurses working with women who have experienced incarceration and their children, both in custodial and community settings.