Treated

Distribution by Scientific Domains
Distribution within Medical Sciences

Terms modified by Treated

  • treated animals
  • treated area
  • treated cell
  • treated child
  • treated dog
  • treated effluent
  • treated embryo
  • treated eye
  • treated fabric
  • treated fish
  • treated fruit
  • treated group
  • treated groups
  • treated heart
  • treated hypertension
  • treated leaf
  • treated lesion
  • treated male
  • treated mouse
  • treated patient
  • treated plant
  • treated rat
  • treated sample
  • treated seed
  • treated sewage effluent
  • treated site
  • treated skin
  • treated subject
  • treated surface
  • treated tumor
  • treated wastewater
  • treated water
  • treated woman

  • Selected Abstracts


    Long-Term Posttreatment Functioning Among Those Treated for Alcohol Use Disorders

    ALCOHOLISM, Issue 2 2006
    Patrick R. Clifford
    This article summarizes the proceedings of a symposium that was organized and chaired by Patrick R. Clifford and presented at the 2005 Research Society on Alcoholism meeting in Santa Barbara, California. The aims of the presentation were to focus on the prediction and explanation of longer-term functioning following alcohol use disorders (AUD) treatment. Along these lines, Stephen A. Maisto, PhD, presented data (i.e., Project MATCH outpatient sample) on the relationship between drinking behavior in the first year following AUD outpatient treatment initiation and functioning at 3-year follow-up. Robert L. Stout, PhD, using data from the Extended Case Monitoring Study, analyzed long-term drinking patterns using shorter-term information. James R. McKay, PhD, examined the relationship between treatment services received and problem severities across a 2-year follow-up period. J. Scott Tonigan, PhD, served as the panel discussant. [source]


    Effect of root surface treatment with propolis and fluoride in delayed tooth replantation in rats

    DENTAL TRAUMATOLOGY, Issue 6 2008
    Jéssica Lemos Gulinelli
    Nevertheless, an extended extraoral period damages the periodontal ligament and results in external root resorption. The purpose of this study was to assess by histologic and histometric analysis, the influence of propolis 15% (natural resinous substance collected by Apis mellifera bees from various plants) and the fluoride solution used as root surface treatment on the healing process after delayed tooth replantation. Thirty Wistar (Rattus norvegicus albinus) rats were submitted to extraction of their upper right incisor. The teeth were maintained in a dry environment for 60 min. After this, the pulp was extirpated and the papilla, enamel organ and periodontal ligament were removed with scalpel. The teeth were divided into three experimental groups: Group I , teeth immersed in 20 ml of physiologic saline; Group II , teeth immersed in 20 ml of 2% acidulated phosphate sodium fluoride; Group III , teeth immersed in 20 ml of 15% propolis. After 10 min of immersion in the solutions, the root canals were dried and filled with calcium hydroxide paste and the teeth were replanted. The animals were euthanized 60 days after replantation. The results showed that similar external root resorption was seen in the propolis and fluoride groups. Teeth treated with physiologic saline tended to have more inflammatory root resorption compared with those treated with fluoride or propolis. However, the comparative analysis did not reveal statistically significant differences (P > 0.05) between the treatment modalities when used for delayed tooth replantation. [source]


    A randomized controlled study of paroxetine and cognitive-behavioural therapy for late-life panic disorder

    ACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2010
    G.-J. Hendriks
    Hendriks G-J, Keijsers GPJ, Kampman M, Oude Voshaar RC, Verbraak MJPM, Broekman TG, Hoogduin CAL. A randomized controlled study of paroxetine and cognitive-behavioural therapy for late-life panic disorder. Objective:, To examine the effectiveness of paroxetine and cognitive-behavioural therapy (CBT) in elderly patients suffering from panic disorder with or without agoraphobia (PD(A)). Method:, Forty-nine patients aged 60+ years with confirmed PD(A) were randomly assigned to 40 mg paroxetine, individual CBT, or to a 14-week waiting list. Outcomes, with avoidance behaviour and agoraphobic cognitions being the primary measures, were assessed at baseline and at weeks 8, 14 (conclusion CBT/waiting list), and at week 26 (treated patients only) and analysed using mixed models. Results:, All outcome measures showed that the patients having received CBT and those treated with paroxetine had significantly better improvement compared with those in the waiting-list condition. With one patient (1/20, 5%) in the CBT and three (3/14, 17.6%) in the paroxetine condition dropping out, attrition rates were low. Conclusion:, Patients with late-life panic disorder respond well to both paroxetine and CBT. Although promising, the outcomes warrant replication in larger study groups. [source]


    Treatment of Vitiligo on Difficult-to-Treat Sites Using Autologous Noncultured Cellular Grafting

    DERMATOLOGIC SURGERY, Issue 1 2009
    SANJEEV V. MULEKAR MD
    BACKGROUND Because of the limitations of medical treatment, various surgical therapies have been developed and are being accepted to treat vitiligo. However, certain areas such as the fingers and toes, palms and soles, lips, eyelids, nipples and areolas, elbows and knees, and genitals are considered difficult-to-treat areas. OBJECTIVE To evaluate data pertaining to individual sites considered to be difficult to treat and highlight that noncultured melanocyte,keratinocyte transplantation (MKT) does not require any special precautions to treat these anatomical sites. METHODS AND MATERIALS Forty patients (13 male and 27 female) with bilateral vitiligo and nine (4 male and 5 female) with unilateral vitiligo were treated using noncultured MKT, for "difficult-to-treat" sites at the National Center for Vitiligo and Psoriasis, Riyadh, Saudi Arabia, and were analyzed for response according to region. Repigmentation was graded as excellent with 95% to 100% pigmentation, good with 65% to 94%, fair with 25% to 64%, and poor with 0% to 24% of the treated area. RESULTS For bilateral vitiligo, more than 50% of patients treated for difficult sites showed more than 65% repigmentation of the treated areas. For unilateral vitiligo, all of the patients except for two treated for the eyelids showed more than 65% repigmentation of the treated area. CONCLUSIONS The concept of a "difficult-to-treat site" is a relative term and depends upon the technique used. The noncultured MKT does not require any special precautions to treat these anatomical sites. This review may help physicians to change the concept of "difficult-to-treat site." [source]


    Use of Honey as an Adjunct in the Healing of Split-Thickness Skin Graft Donor Site

    DERMATOLOGIC SURGERY, Issue 2 2003
    Aykut Misirlioglu MD
    BACKGROUND Different techniques are being used in treatment of split-thickness skin graft donor sites; however, there is not a widely accepted method established for these partial-thickness wounds. It is well known that honey has been very effective in the treatment of various types of wounds, but there is not any information about the usage of honey as split-thickness skin graft donor site dressing in the literature. OBJECTIVE To evaluate and compare the effectiveness of honey-impregnated gauzes, hydrocolloid dressings, and as a conventional dressing, saline-soaked gauzes for skin graft donor sites. METHODS This is a nonrandomized, prospective, open-label (noncontrolled), side-by-side comparison trial of various options that are available for second-intention healing of donor site for split-thickness skin grafts. Eighty-eight patients who underwent skin grafting were observed using two different groups. In the first group, the donor site was divided into two equal halves, with each half being treated with honey-soaked gauzes and the other half with paraffin gauzes (group 1A), hydrocolloid dressings (group 1B), and saline-soaked gauzes (group 1C) alternatively. In the second group, two separate donor sites were formed, with one of them being treated with honey-impregnated gauzes (groups 2A,C) and the other one treated with either paraffin gauzes (group 2A), hydrocolloid dressings (group 2B), or saline-soaked gauzes (group 2C). The healing time, rate of infection, and sense of pain were evaluated. RESULTS In the treatment of split-thickness skin graft donor sites, honey-impregnated gauzes showed faster epithelization time and a low sense of pain than paraffin gauzes and saline-soaked gauzes. There was no significant difference between honey-impregnated gauzes and hydrocolloid dressings with regard to epithelization time and sense of pain. CONCLUSION The use of honey-impregnated gauzes is effective, safe, and practical. Honey can be an alternative material for the split-thickness skin graft donor site treatment. [source]


    Treatment of Pigmented Hypertrophic Scars with the 585 nm Pulsed Dye Laser and the 532 nm Frequency-Doubled Nd:YAG Laser in the Q-Switched and Variable Pulse Modes: A Comparative Study

    DERMATOLOGIC SURGERY, Issue 8 2002
    Leyda Elizabeth Bowes MD
    background. Pigmented hypertrophic scars are a difficult condition to treat. They may result from traumatic injuries or from surgical and cosmetic procedures. The 585 nm flashlamp-pumped pulsed dye laser (FLPDL) has been used to treat this condition, with significant improvement of varying degrees. It remains to be determined whether other laser modalities may have a similar or even greater success in the treatment of pigmented hypertrophic scars. objective. To determine the efficacy of the 532 nm frequency-doubled Nd:YAG laser in the treatment of pigmented hypertrophic scars as compared to the 585 nm FLPDL. methods. Six patients with pigmented hypertrophic scars and skin phototypes II,IV were chosen. A scar was selected for treatment in each patient and divided into four equal 2 cm segments. Three segments were each treated with a different laser modality and one was left untreated to serve as the control. A 585 nm FLPDL was used with an energy of 3.5 J, a pulse duration of 450 ,sec, and a 10 mm spot size. A 532 nm Q-switched frequency-doubled Nd:YAG laser was set to an energy of 2.8 J, a 10-nsec pulse, and a 3 mm spot size. The same 532 nm laser was set to the variable pulse mode to treat a 2 cm scar segment, with an energy of 9.5 J, a 10-msec pulse, and a 4 mm spot size. An average of 3.3 treatments were performed on each scar segment, at intervals of 4,6 weeks and long-term follow-up at 22 weeks. Treatment outcome was graded by a blind observer using the Vancouver General Hospital (VGH) Burn Scar Assessment Scale. A SigmaStat t -test was used to determine the statistical significance of the values obtained. results. Treatment of pigmented hypertrophic scars with the 532 nm Q-switched Nd:YAG laser led to a significant improvement of 38% in the VGH scores when compared to baseline (P = .005). The 585 nm FLPDL also had a favorable effect on the scars, with an average improvement of 36.1% in the VGH scores. There was no significant difference noted between the outcome of treatment with either of these two lasers. Treatment with the 532 nm variable pulse Nd:YAG laser led to a 19% improvement in the VGH scores of scars, which did not differ significantly from the 16.1% improvement observed in control scars on the last follow-up visit. No side effects or complications from treatment were noted or reported during the course of the study. At the conclusion of the study, five of six patients chose the segment treated with the 532 nm Q-switched Nd:YAG laser as the best segment overall. conclusion. The 532 nm Q-switched Nd:YAG laser and the 585 nm FLPDL offer comparable favorable results in the treatment of pigmented hypertrophic scars. The 532 nm Q-switched Nd:YAG laser may be preferred by patients particularly distressed by the dark color of their scars. [source]


    Occlusive Dressing versus Oxygen Mist Therapy Following CO2 Laser Resurfacing

    DERMATOLOGIC SURGERY, Issue 6 2000
    Teri Onouye BA
    Background. Oxygen is an essential element for collagen synthesis and reepithelialization. The use of topical oxygen after CO2 laser resurfacing has not been studied. Objective. To compare the rate and quality of healing in wounds treated with an oxygen mist to those treated with occlusive dressing following CO2 laser resurfacing. Methods. Three patients underwent CO2 laser resurfacing to each half of the face 3 weeks apart. Postoperatively, half of the face was treated with an oxygen mist protocol for 5 days, while the other half was treated with occlusive dressing for 4 days. Results. At postoperative day 5, significantly less crusting was observed on the half of the face treated with the oxygen mist protocol (p < 0.05). Conclusion. The oxygen mist postoperative protocol may offer patients similar overall healing rates and significantly less crusting compared to occlusive dressing. [source]


    Protein tyrosine phosphatases in Chaetopterus egg activation

    DEVELOPMENT GROWTH & DIFFERENTIATION, Issue 5-6 2003
    Shantá D. Hinton
    Changes in protein tyrosine phosphorylation are an essential aspect of egg activation after fertilization. Such changes result from the net contributions of both tyrosine kinases and phosphatases (PTP). This study was conducted to determine what role(s) PTP may have in egg activation. We identified four novel PTP in Chaetopterus pergamentaceus oocytes, cpPTPNT6, cpPTPNT7, cpPTPR2B, and cpPTPR2A, that have significant homology to, respectively, human PTP,, -,, -D2 and -BAS. The first two are cytosolic and the latter two are transmembrane. Several PTP inhibitors were tested to see if they would affect Chaetopterus pergamentaceus fertilization. Eggs treated with ,-bromo-4-hydroxyacetophenone (PTP inhibitor 1) exhibited microvillar elongation, which is a sign of cortical changes resulting from activation. Those treated with Na3VO4 underwent full parthenogenetic activation, including polar body formation and pseudocleavage and did so independently of extracellular Ca2+, which is required for the Ca2+ oscillations that initiate development after fertilization. Fluorescence microscopy identified phosphotyrosine-containing proteins in the cortex and around the nucleus of vanadate-activated eggs, whereas in fertilized eggs they were concentrated only in the cortex. Immunoblots of vanadate-activated and fertilized eggs showed tyrosine hyperphosphorylation of approximately140 kDa protein. These results suggest that PTP most likely maintain the egg in an inactive state by dephosphorylation of proteins independent of the Ca2+ oscillations in the activation process. [source]


    In vitro organogenesis of pancreas in Xenopus laevis dorsal lips treated with retinoic acid

    DEVELOPMENT GROWTH & DIFFERENTIATION, Issue 2 2000
    Naomi Moriya
    Dorsal lips of Xenopus laevis may differentiate into pancreas after treatment with retinoic acid in vitro. The dorsal lip region is fated to be dorsal mesoderm and anterior endoderm. Dorsal lip cells isolated from stage 10 early gastrula differentiate into tissues such as notochord, muscle and pharynx. However, in the present study, dorsal lips treated with 10,4M retinoic acid for 3 h differentiated into pancreas-like structures accompanied by notochord and thick endodermal epithelium. Sections of the explants showed that some cells gathered and formed an acinus-like structure as observed under microscopes. In addition to the morphological changes, expressions of the pancreas-specific molecular markers, XlHbox8 and insulin, were induced in retinoic acid-treated dorsal lip explants. Therefore, it is suggested that retinoic acid may induce the dorsal lip cells to differentiate into a functional pancreas. However, continuous treatment with retinoic acid did not induce pancreas differentiation at any concentration. Dorsal lips treated with retinoic acid within 5 h after isolation differentiated into pancreas-like cells, while those treated after 15 h or more did not. The present study provided a suitable test system for analyzing pancreas differentiation in early vertebrate development. [source]


    Social context affects testosterone-induced singing and the volume of song control nuclei in male canaries (Serinus canaria)

    DEVELOPMENTAL NEUROBIOLOGY, Issue 10 2006
    Géraldine Boseret
    Abstract The contribution of social factors to seasonal plasticity in singing behavior and forebrain nuclei controlling song, and their interplay with gonadal steroid hormones are still poorly understood. In many songbird species, testosterone (T) enhances singing behavior but elevated plasma T concentrations are not absolutely required for singing to occur. Singing is generally produced either to defend a territory or to attract a mate and it is therefore not surprising that singing rate can be influenced by the sex and behavior of the social partner. We investigated, based on two independent experiments, the effect of the presence of a male or female partner on the rate of song produced by male canaries. In the first experiment, song rate was measured in dyads composed of one male and one female (M-F) or two males (M-M). Birds were implanted with T-filled Silastic capsules or with empty capsules as control. The number of complete song bouts produced by all males was recorded during 240 min on week 1, 2, 4, and 8 after implantation. On the day following each recording session, brains from approximately one-fourth of the birds were collected and the volumes of the song control nuclei HVC and RA were measured. T increased the singing rate and volume of HVC and RA but these effects were affected by the social context. Singing rates were higher in the M-M than in the M-F dyads. Also, in the M-M dyads a dominance-subordination relationship soon became established and dominant males sang at higher rates than subordinates in T-treated but not in control pairs. The differences in song production were not reflected in the size of the song control nuclei: HVC was larger in M-F than in M-M males and within the M-M dyads, no difference in HVC or RA size could be detected between dominant and subordinate males. At the individual level, the song rate with was positively correlated with RA and to a lower degree HVC volume, but this relationship was observed only in M-M dyads, specifically in dominant males. A second experiment, carried out with castrated males that were all treated with T and exposed either to another T-treated castrate or to an estradiol-implanted female, confirmed that song rate was higher in the M-M than in the M-F condition and that HVC volume was larger in heterosexual than in same-sex dyads. The effects of T on singing rate and on the volume of the song control nuclei are thus modulated by the social environment, including the presence/absence of a potential mate and dominance status among males. 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source]


    Unlocking the opportunity of tight glycaemic control

    DIABETES OBESITY & METABOLISM, Issue 2005
    Inhaled insulin: clinical efficacy
    Numerous attempts have been made to develop novel routes of insulin delivery that are both effective and tolerable. Of all the potential non-invasive delivery options, pulmonary delivery is the most clinically viable. Early studies demonstrate that the inhaled insulin is rapidly absorbed and is closer to biological insulin than standard subcutaneous insulin (SC). To date, inhaled insulin (Exubera®) has been clinically assessed in more than 3500 patients with type 1 or type 2 diabetes, some treated for more than 7 years. Several phase 3 studies of 24-week duration have demonstrated comparable glycosylated haemoglobin (HbA1c) control in patients with type 1 diabetes treated with Exubera® vs. SC insulin. Similar results have also been recorded in patients with type 2 diabetes. Furthermore, Exubera® has shown clinical superiority to oral agent regimens in patients with type 2 diabetes who failed to achieve their target HbA1c using lifestyle modification and oral agents. Exubera® was well tolerated and treatment satisfaction was high, with Exubera® being the preferred insulin therapy in all studies. The results of these trials, and others, suggest that Exubera® may be a valuable tool to help a wide variety of patients with type 1 or type 2 diabetes reach their recommended goals for glycaemic control, irrespective of their current therapy. [source]


    Letrozole normalizes serum testosterone in severely obese men with hypogonadotropic hypogonadism

    DIABETES OBESITY & METABOLISM, Issue 3 2005
    H. De Boer
    Background:, Morbid obesity is associated with increased estradiol production as a result of aromatase-dependent conversion of testosterone to estradiol. The elevated serum estradiol levels may inhibit pituitary LH secretion to such extent that hypogonadotropic hypogonadism can result. Normalization of the disturbed estradiol-testosterone balance may be beneficial to reverse the adverse effects of hypogonadism. Aim:, To examine whether aromatase inhibition with Letrozole can normalize serum testosterone levels in severely obese men with hypogonadotropic hypogonadism. Patients and Methods:, Ten severely obese men, mean age 48.2 ± 2.3 (s.e.) years and body mass index 42.1 ± 2.6 kg/m2, were treated with Letrozole for 6 weeks in doses ranging from 7.5 to 17.5 mg per week. Results:, Six weeks of treatment decreased serum estradiol from 120 ± 20 to 70 ± 9 pmol/l (p = 0.006). None of the subjects developed an estradiol level of less than 40 pmol/l. LH increased from 4.5 ± 0.8 to 14.8 ± 2.3 U/l (p < 0.001). Total testosterone rose from 7.5 ± 1.0 to 23.8 ± 3.0 nmol/l (p < 0.001) without a concomitant change in sex hormone-binding globulin level. Those treated with Letrozole 17.5 mg per week had an excessive LH response. Conclusion:, Short-term Letrozole treatment normalized serum testosterone levels in all obese men. The clinical significance of this intervention remains to be established in controlled, long-term studies. [source]


    Comparing hormonal and symptomatic responses to experimental hypoglycaemia in insulin- and sulphonylurea-treated Type 2 diabetes

    DIABETIC MEDICINE, Issue 7 2009
    P. Choudhary
    Abstract Aims, Patients with diabetes rely on symptoms to identify hypoglycaemia. Previous data suggest patients with Type 2 diabetes develop greater symptomatic and hormonal responses to hypoglycaemia at higher glucose concentrations than non-diabetic controls and these responses are lowered by insulin treatment. It is unclear if this is as a result of insulin therapy itself or improved glucose control. We compared physiological responses to hypoglycaemia in patients with Type 2 diabetes patients treated with sulphonylureas (SUs) or insulin (INS) with non-diabetic controls (CON). Methods, Stepped hyperinsulinaemic hypoglycaemic clamps were performed on 20 subjects with Type 2 diabetes, 10 SU-treated and 10 treated with twice-daily premixed insulin, and 10 age- and weight-matched non-diabetic controls. Diabetic subjects were matched for diabetes duration, glycated haemoglobin (HbA1c) and hypoglycaemia experience. We measured symptoms, counterregulatory hormones and cognitive function at glucose plateaux of 5, 4, 3.5, 3 and 2.5 mmol/l. Results, Symptomatic responses to hypoglycaemia occurred at higher blood glucose concentrations in SU-treated than INS-treated patients [3.5 (0.4) vs. 2.6 (0.5) mmol/l SU vs. INS; P = 0.001] or controls [SU vs. CON 3.5 (0.4) vs. 3.0 (0.6) mmol/l; P = 0.05]. They also had a greater increase in symptom scores at hypoglycaemia [13.6 (11.3) vs. 3.6 (6.1) vs. 5.1 (4.3) SU vs. INS vs. CON; P = 0.017]. There were no significant differences in counterregulatory hormone responses or impairment of cognitive function among groups. Conclusions, Sulphonylurea-treated subjects are more symptomatic of hypoglycaemia at a higher glucose level than insulin-treated subjects. This may protect them from severe hypoglycaemia but hinder attainment of glycaemic goals. [source]


    Treatment retention in adolescent patients treated with methadone or buprenorphine for opioid dependence: a file review

    DRUG AND ALCOHOL REVIEW, Issue 2 2006
    JAMES BELL
    Abstract The aim of this study was to compare retention and re-entry to treatment between adolescent subjects treated with methadone, those treated with buprenorphine, and those treated with symptomatic (non-opioid) medication only. We used a retrospective file review of all patients aged less than 18 at first presentation for treatment for opioid dependence. The study was conducted at the Langton Centre, Sydney, Australia, an agency specialising in the treatment of alcohol and other drug dependency. Sixty-one adolescents (age range 14,17 years at the time of commencing treatment); mean reported age of initiation of heroin use was 14 ± 1.3 years (range 11,16). Sixty-one per cent were female. The first episode of treatment was methadone maintenance in 20 subjects, buprenorphine in 25, symptomatic medication in 15; one patient underwent assessment only. These 61 subjects had a total of 112 episodes of treatment. Subjects treated with methadone had significantly longer retention in first treatment episode than subjects treated with buprenorphine (mean days 354 vs. 58, p<0.01 by Cox regression) and missed fewer days in the first month (mean 3 vs. 8 days, p<0.05 by t-test). Subsequent re-entry for further treatment occurred in 25% of subjects treated with methadone, 60% buprenorphine and 60% symptomatic medications. Time to reentry after first episode of buprenorphine treatment was significantly shorter than after methadone treatment (p < 0.05 by Kaplan-Meier test). Methadone maintenance appears to have been more effective than buprenorphine at preventing premature drop-out from treatment of adolescent heroin users. [source]


    Evaluation of river water genotoxicity using the piscine micronucleus test

    ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 6 2007
    Serap Ergene
    Abstract The Berdan River, which empties into the Mediterranean Sea on the east coast of Turkey, receives discharges of industrial and municipal waste. In the present study, the in vivo piscine micronucleus (MN) test was used to evaluate the genotoxicity of water samples collected from different locations along the Berdan River. Nile tilapia (Oreochromis niloticus) were exposed in the laboratory for 2, 4, and 6 days, and micronuclei were evaluated in peripheral blood erythrocytes, gill cells, and caudal fin epithelial cells. A single dose of 5 mg/L cyclophosphamide was used as a positive control. In addition to micronuclei, nuclear abnormalities (NAs), such as binucleated cells and blebbed, notched, and lobed nuclei, were assessed in the erythrocytes, and chemical analyses were carried out to determine the amount of heavy metals in the water samples. MN and NA frequencies were significantly elevated (up to 2- to 3-fold) in fish exposed to river water samples taken downstream of potential discharges, and the elevated responses in gill and fin cells were related to the concentration of heavy metals in the water. MN frequencies (expressed as micronucleated cells/1,000 cells), in both treated and untreated fish, were greatest in gill cells (range: 0.80,3.70), and generally lower in erythrocytes (range: 0.50,2.80), and fin cells (range: 0.45,1.70). The results of this study indicate that the Berdan River is contaminated with genotoxic pollutants and that the genotoxicity is related to the discharge of wastes into the river water. Environ. Mol. Mutagen., 2007. © 2007 Wiley-Liss, Inc. [source]


    Acute exposure of human lung cells to 1,3-butadiene diepoxide results in G1 and G2 cell cycle arrest

    ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2005
    Michael Schmiederer
    Abstract 1,3-butadiene (BD) causes genetic damage, including adduct formation, sister chomatid exchange, and point mutations. Previous studies have focused on the types of genetic damage and tumors found after long-term exposure of rodents to butadiene. This study examined the effect of the most active BD metabolite, butadiene diepoxide (BDO2), on cell cycle entry and progression in human lung fibroblasts (LU cells) with a normal diploid karyotype. Serum-arrested (G0) LU cells were exposed to BDO2 for 1 hr and stimulated to divide with medium containing 10% fetal bovine serum. The BDO2 -treated LU cells were evaluated for cell cycle progression, nuclear localization of arrest mediators, mitotic index, and cellular proliferation. The BDO2 -treated cells demonstrated a substantial inhibition of cell proliferation when treated with 100 ,M BDO2 for 1 hr. No appreciable levels of apoptosis or mitotic figures were observed in the BDO2 -treated cells through 96 hr posttreatment. Flow cytometric analysis revealed that the lack of proliferation in BDO2 -treated LU cells was related to G1 arrest in about half of the cells and a delayed progression through S and G2 arrest in nearly all of the remaining cells. Both G1 and G2 arrest were prolonged and only a very small percentage of BDO2 -treated cells were eventually able to replicate. Increased nuclear localization of both p53 and p21cip1 was observed in BDO2 -treated cells, suggesting that the cell cycle arrest was p21cip1 -mediated. These results demonstrate that BDO2 induces cell cycle perturbation and arrest even with short-term exposure that does not produce other pathologic cellular effects. Environ. Mol. Mutagen., 2005. © 2005 Wiley-Liss, Inc. [source]


    Evaluating wastewater-induced plant genotoxicity using randomly amplified polymorphic DNA

    ENVIRONMENTAL TOXICOLOGY, Issue 1 2008
    K. M. Swaileh
    Abstract Wastewater often contains genotoxic substances that can resist different stages of the treatment process. In the present study, randomly amplified polymorphic DNA technology was applied to evaluate the genotoxic effects of wastewater (treated and raw) irrigation on oat plants (Avena sativa). RAPD profiles obtained showed that both treated and raw wastewater (RWW) were having genotoxic effects on oat plants. This was apparent by the appearance/disappearance of bands in the treatments compared with the control plants. From the 15 primers used, 186 bands were obtained with an average of 12.4 bands per primer. Irrigating plants with RWW caused 51 new bands to appear and 19 to disappear. Treated wastewater (TWW) caused only 16 new bands and the loss of 17 bands. This makes TWW less genotoxic than RWW. The Euclidean distances shown on the dendrogram, revealed the presence of two clusters according to dissimilarity values. One cluster contained the control plants and those irrigated with TWW, whereas the second contained the plants irrigated with RWW. Similarity indices calculated between the treatments and the control plants showed that the control and the plants irrigated with TWW had a similarity index of 0.87, the control and plants irrigated with RWW 0.73 and between the treatments 0.75. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008. [source]


    Influence of isolation on the recovery of pond mesocosms from the application of an insecticide.

    ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2007

    Abstract The influence of relative isolation on the ecological recovery of freshwater outdoor mesocosm communities after an acute toxic stress was assessed in a 14-month-long study. A single concentration of deltamethrin was applied to 8 out of 16 outdoor 9-m3 mesocosms to create a rapid decrease of the abundance of arthropods. To discriminate between external and internal recovery mechanisms, four treated and four untreated (control) mesocosms were covered with 1-mm mesh screen lids. The dynamics of planktonic communities were monitored in the four types of ponds. The abundance of many phytoplankton taxa increased after deltamethrin addition, but the magnitude of most increases was relatively small, probably due to low nutrient availability and the survival of rotifers. The greatest impact on zooplankton was seen in Daphniidae and, to a lesser extent, calanoid copepods. Recovery (defined as when statistical analysis failed to detect a difference in the abundance between the deltamethrin-treated ponds and corresponding control ponds for two consecutive sampling dates) of Daphniidae was observed in the water column 105 and 77 d after deltamethrin addition in open and covered mesocosms, respectively, and <42 d for both open and covered ponds at the surface of the sediments. Rotifers did not proliferate, probably because of the survival of predators (e.g., cyclopoid copepods). These results confirm that the recovery of planktonic communities after exposure to a strong temporary chemical stress mostly depends upon internal mechanisms (except for larvae of the insect Chaoborus sp.) and that recovery dynamics are controlled by biotic factors, such as the presence of dormant forms and selective survival of predators. [source]


    Biochemical and histopathological effects in pearl dace (Margariscus margarita) chronically exposed to a synthetic estrogen in a whole lake experiment

    ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2006
    Vince P. Palace
    Abstract Potential effects of exposure to the synthetic estrogen 17,-ethynylestradiol (EE2) were examined in several species of fish from a lake experimentally treated with environmentally relevant concentrations of the contaminant. Ethynylestradiol was added to Lake 260, a small Precambrian shield lake at the Experimental Lakes Area in northwestern Ontario, Canada, from May to October of 2001, 2002, and 2003. Mean concentrations of EE2 in epilimnetic waters ranged between 4.5 and 8.1 ng/L during the three years, with overall means of 6.1 (±2.8), 5.0 (±1.8), and 4.8 (±1.0) ng/L for the three years, respectively. Male and female pearl dace (Margariscus margarita) captured after EE2 additions began contained up to 4,000-fold higher concentrations of the egg yolk precursor vitellogenin than fish captured from the same lake before the EE2 additions or when compared to fish from reference lakes. Edema in the ovaries, inhibited development of testicular tissue, intersex, and histopathological kidney lesions were all evident in fish exposed to EE2. Some indications that EE2 exposure affected in vitro steroidogenic capacity of the ovaries and the testes existed, although results were not always consistent between years. Pearl dace abundance was similar in the lake treated with EE2 and the reference lake. A trend exists toward a reduced overall population of pearl dace from the treated and reference lakes, as do indications that young-of-the-year size classes are less abundant in the EE2-treated lake. Biochemical and histopathological impacts observed in fish exposed to EE2 in this study have not yet been linked to clear population level impacts in pearl dace. Monitoring of these populations is ongoing. [source]


    Effects of fungicides on thyroid function, metabolism, and thermoregulation in cotton rats,

    ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2001
    Thomas E. Tomasi
    Abstract Among the myriad of recent studies on endocrine-disrupting chemicals, relatively few involve thyroid disruption, and most of these address exposure/disruption during embryonic life. Of those involving adult vertebrates, the endpoints examined are thyroid measurements. Even though thyroid disruption could potentially interfere with energy metabolism and thermoregulation such that over-winter survival might be compromised, the possible energetic consequences of these thyroid perturbations have not been investigated. We assessed thyroid function and measured resting metabolic rates of cotton rats chronically exposed to the fungicides vinclozolin or mancozeb. In addition, we measured norepinephrine-induced nonshivering thermogenesis and cold-induced thermogenesis and then cold-acclimated the mancozeb animals. Although thyroid hormone concentrations generally decreased, this was compensated for by an increase in thyroxine turnover (vinclozolin study only) such that thyroxine utilization rate was not different. In addition, there was no difference between the treated and control animals in any of the metabolic parameters measured. It is concluded that wild rodents exposed to these compounds are not energetically compromised. [source]


    Comparison of unfractioned and low molecular weight heparin for prophylaxis of coagulopathies in 52 horses with colic: a randomised double-blind clinical trial

    EQUINE VETERINARY JOURNAL, Issue 5 2003
    K. FEIGE
    Summary Reasons for performing study: Unfractioned heparin (UFH) is widely used for prophylaxis of coagulation disorders, especially in colic-affected horses. However, it is accompanied by certain side effects. Objectives: To compare the efficacy and side effects of unfractioned and low molecular weight heparin (LMWH) in horses with colic. Methods: The study was carried out as a randomised, double-blind, controlled clinical trial. Fifty-two horses with colic were treated subcutaneously with either UFH (heparin calcium, 150 iu/kg bwt initially, followed by 125 iu/kg bwt q. 12 h for 3 days and then 100 iu/kg bwt q. 12 h) or LMWH (dalteparin, 50 iu/kg bwt q. 24 h). All horses underwent daily physical examination including assessment of jugular veins, local reaction to heparin injections, haematological evaluation and coagulation profiles over up to 9 days. Results: The type of heparin used did not affect the general behaviour and condition. There were significantly more jugular vein changes in horses treated with UFH. Packed cell volume decreased significantly within the first few days of UFH treatment, but did not change significantly in horses treated with LMWH. Activated partial thromboplastin time (aPTT) and thrombin time (TT) were prolonged in horses treated with UFH but not in those treated with LMWH. Conclusions: It was concluded that, in comparison to UFH, LMWH has markedly fewer side effects in horses. Potential relevance: Therefore, LMWH is recommended for prophylaxis of coagulation disorders in colic patients. [source]


    Arthroscopic laser extirpation of metacarpophalangeal synovial pad proliferation in eleven horses

    EQUINE VETERINARY JOURNAL, Issue 3 2001
    D. J. MURPHY
    Summary A new surgical technique for treatment of chronic metacarpophalangeal synovial pad proliferation in the horse and the findings and long-term follow-up from 11 clinical cases are described. The medical records of all equine lameness cases attributed to metacarpophalangeal synovial pad proliferation admitted to the College of Veterinary Medicine at Cornell University (1991,1996) were reviewed and all those treated surgically by laser extirpation were included in this study. Retrieved data included subject details, preoperative lameness, ultrasonography, radiography and synovial fluid evaluations and lesion histopathology. Lesions were ablated using a CO2 or a Nd:YAG laser intra-articularly with arthroscopic guidance. Long-term follow-up was provided by telephone conversation with owners or trainers. All horses had fetlock joint effusion and were lame at presentation. Mean synovial pad thickness measured ultrasonographically was 9.0 mm (range 6,15 mm). Seven horses (64%) had radiographic evidence of remodelling of the dorsal cortex of distal McIII and 3 horses (27%) had concurrent dorsal proximal P1 fractures. No postoperative complications were noted. All 11 horses returned to training within 90 days of surgery without recurrence of the lesion(s). Laser extirpation of metacarpophalangeal synovial pad proliferation using arthroscopic guidance provided a rapid, safe and efficient method for surgical removal of such lesions without complications or recurrence. This surgical technique provides a suitable alternative to more conventional treatments for chronic metacarpophalangeal synovial pad proliferation in horses, particularly for removal of very large, fibrotic masses. [source]


    A randomized controlled trial of transcatheter arterial chemoembolization with lipiodol, doxorubicin and cisplatin versus intravenous doxorubicin for patients with unresectable hepatocellular carcinoma

    EUROPEAN JOURNAL OF CANCER CARE, Issue 5 2009
    M. MABED md, professor
    Hepatocellular carcinoma (HCC) is a major and often therapeutically frustrating oncological problem. A total of 100 patients with unresectable HCC were recruited and randomized to be treated with either transcatheter arterial chemoembolization (TACE) or systemic chemotherapy. Fifty patients were treated with TACE using lipiodol, doxorubicin and cisplatin, while 50 patients were treated with systemic doxorubicin alone. Patients treated with TACE achieved a significantly higher response rate, with partial response achieved in 16 patients (32%) versus five patients (10%) in the chemotherapy arm (P = 0.007). A significantly more favourable tumour response to chemoembolization was found in patients with single lesions (P = 0.02), Child class A (P = 0.007), Okuda stage 1 (P = 0.005) and ,-feto protein less than 400 ng/mL (P < 0.001). The probability of tumour progression was significantly lower in cases treated with TACE where the median progression free survival was 32 weeks (range, 16,70 weeks) versus 26 weeks (range, 14,54 weeks) for patients treated with systemic chemotherapy (P = 0.03). However, the median overall survival did not differ significantly in cases treated with TACE (38 weeks) compared with those treated with chemotherapy (32 weeks) (P = 0.08), except for patients with serum albumin >3.3 g/dL (60 vs. 36 weeks; P = 0.003). Multivariate Cox regression analysis showed that a rise of serum albumin by 1 g/dL is associated with a decrease in the risk of death by 33% (95% confidence interval: 0.12,0.94, P = 0.038). Mortality in the chemoembolization arm was due to tumour progression in 18 patients (53%), liver failure in 11 patients (32%) and gastro intestinal tract (GIT) bleeding in 5 patients (15%). Mortality in the chemotherapy arm was due to tumour progression in 23 patients (64%), liver failure in 9 patients (25%) and GIT bleeding in 4 patients (11%). Treatment-related mortality was 4% in the TACE arm versus 0% in the chemotherapy arm. In conclusion, the overall survival benefits of TACE and systemic doxorubicin are similar for patients with unresectable HCC amenable to either treatment. It is crucial to optimize the benefit,risk ratio of TACE. In this setting, serum albumin level is a candidate marker for selection of cases who may benefit from this procedure. [source]


    Medium-term results of percutaneous vertebroplasty in multiple myeloma

    EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2006
    Luis Ramos
    Abstract:, Vertebral compression fractures (VCFs) are common in multiple myeloma (MM). Percutaneous vertebroplasty (PVP) is used to stabilize vertebral collapse and treat the pain. Few studies have been carried out on PVP in MM and follow-up has tended to be short. We have prospectively evaluated the safety and efficacy of PVP in the VCFs resulting from MM or plasmacytomas. Nineteen PVP were performed in 12 consecutive patients. We monitored their pain and functional status using visual analog (VAS) and Eastern Cooperative Oncology Group (ECOG) scale, respectively. For a subjective assessment, every patient was asked about his/her degree of satisfaction. The mean age of the participants was 66 yr. Significant improvement occurred 1 d after PVP according to the VAS score (7.5 pre-PVP to 3.7, P < 0.0001) and ECOG assessment (3.1 to 2.5, P = 0.002). This significant improvement was maintained after 3.2 yr of follow-up. Sixty-three percent of patients were highly satisfied with the result of the PVP and 37% were satisfied. The peri-operative mortality was 0%. Leakage of the cement outside of the vertebral body was noted in 16 of 19 injected vertebrae (84%) but none of the patients developed any clinical or neurological symptoms. At the last follow-up, no further collapse in the treated or neighboring vertebrae was noted. VCFs caused by MM or plasmacytomas can be effectively treated by vertebroplasty. PVP is associated with early clinical improvement of pain and function and can be maintained after a long follow-up without major procedure-related complications. [source]


    Blood morphine levels in naltrexone-exposed compared to non-naltrexone-exposed fatal heroin overdoses

    ADDICTION BIOLOGY, Issue 3 2003
    DIANE ARNOLD-REED
    The aim of this study was to investigate the association between prior exposure to naltrexone and increased risk of fatal heroin overdose using a review of toxicology reports for heroin-related fatalities between July 1997 to August 1999 for two groups: those treated with oral naltrexone and those who were not treated. Additional information for the oral naltrexone group was obtained from clinic files. Naltrexone-treated deaths were identified from the patient database at the Australian Medical Procedures Research Foundation (AMPRF), Perth, Western Australia (WA) through the Western Australian Department of Health, Data Linkage Project. Non-treated cases were identified from the database at the Forensic Science Laboratory, State Chemistry Centre (WA). We identified and investigated blood morphine concentrations following 21 fatal heroin overdoses with prior exposure to naltrexone and in 71 non-naltrexone-exposed cases over the same time period. The proportion of deaths where heroin use was a major contributing factor was little different in the non-naltrexone compared to the naltrexone-exposed group. Furthermore, in ,acute opiate toxicity' deaths, blood morphine levels were lower in non-naltrexone-exposed compared with naltrexone-exposed cases. Although there was a higher number of deaths designated as rapid (i.e. occurring within 20 minutes) in the naltrexone-exposed (89%) compared with the non-exposed group (72%) this was not statistically significant. Other drug use in relation to heroin-related fatalities is discussed. Findings do not support the hypothesis that prior exposure to naltrexone increases sensitivity to heroin toxicity. [source]


    In vitro fracture behavior of maxillary premolars with metal crowns and several post-and-core systems

    EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 3 2006
    Wietske A. Fokkinga
    The in vitro fracture behavior of severely damaged premolars, restored with metal crowns with limited ferrule and several post-and-core systems, was investigated. Crowns of maxillary premolars were removed and canals were prepared with Gates Glidden drills and with Parapost drills. Groups of 11 samples were each treated with cast post-and-cores (Parapost XP, Wironium Plus) (group 1), prefabricated metal posts (Parapost XH) (group 2), prefabricated glass fiber posts (Parapost FiberWhite) (group 3), and custom-made glass fiber posts (EverStick Post) (group 4). Posts and composite cores and metal crowns in groups 2, 3, and 4 were adhesively cemented. Post-and-cores and crowns in group 1 were cemented with phosphate cement. Thermocycling was performed (6,000×, 5,55 °C). Two static load tests (30°) were applied. During the first load test (preloading) no failures occurred. Failure modes from the second load test were categorized into favorable and unfavorable failures. Mean failure loads among the four groups (group 1, 1845 N; group 2, 1718 N; group 3, 1812 N; and group 4, 1514 N) were not significantly different. Unfavorable failures were root fractures and favorable failures were postcrown displacements. No differences in frequencies of unfavorable/favorable failures were seen among the groups. The results suggest that different post-and-core systems have no influence on the fracture behavior of severely damaged premolars restored with metal crowns with limited ferrule. [source]


    Air-Operable, High-Mobility Organic Transistors with Semifluorinated Side Chains and Unsubstituted Naphthalenetetracarboxylic Diimide Cores: High Mobility and Environmental and Bias Stress Stability from the Perfluorooctylpropyl Side Chain

    ADVANCED FUNCTIONAL MATERIALS, Issue 17 2010
    Byung Jun Jung
    Abstract N,N,-bis(3-(perfluoroctyl)propyl)-1,4,5,8-naphthalenetetracarboxylic acid diimide (8,3-NTCDI) was newly synthesized, as were related fluorooctylalkyl-NTCDIs and alkyl-NTCDIs. The 8,3-NTCDI-based organic thin-film transistor (OTFT) on an octadecyltrimethoxysilane (OTS)-treated Si/SiO2 substrate shows apparent electron mobility approaching 0.7 cm2 V -1s -1 in air. The fluorooctylethyl-NTCDI (8,2-NTCDI) and fluorooctylbutyl-NTCDI (8,4-NTCDI) had significantly inferior properties even though their chemical structures are only slightly different, and nonfluorinated decyl and undecyl NTCDIs did not operate predictably in air. From atomic force microscopy, the 8,3-NTCDI active layer deposited with the substrate at 120 °C forms a polycrystalline film with grain sizes >4,m. Mobilities were stable in air for one week. After 100 days in air, the average mobility of three OTFTs decreased from 0.62 to 0.12 cm2 V -1s -1, but stabilized thereafter. The threshold voltage (VT) increased by 15 V in air, but only by 3 V under nitrogen, after one week. On/off ratios were stable in air throughout. We also investigated transistor stability to gate bias stress. The transistor on hexamethlydisilazane (HMDS) is more stable than that on OTS with mobility comparable to amorphous Si TFTs. VT shifts caused by ON (30 V) and OFF (,20 V) gate bias stress for the HMDS samples for 1 hour were 1.79 V and 1.27 V under N2, respectively, and relaxation times of 106 and 107 s were obtained using the stretched exponential model. These performances are promising for use in transparent display backplanes. [source]


    Flame retardancy finish with an organophosphorus retardant on silk fabrics

    FIRE AND MATERIALS, Issue 6 2006
    Jin-Ping Guan
    Abstract The paper mainly deals with flame retardancy of silk fabrics treated with a commercial organophosphorus flame retardant [N-hydroxymethyl (3-dimethyl phosphono) propionamide (HDPP), also known as Pyrovatex CP], using the pad-dry-cure-wash method. The structures and properties of the treated and control sample are discussed. The Limiting Oxygen Index (LOI) value of the modified sample is above 30%. After 50 laundry cycles, it still has some flame retardancy left. HDPP and a cross-linking agent (HMM) were bound to silk fabrics which is confirmed by FT-IR spectra and amino analysis. The reaction degree of the flame retardant with silk is also high; almost all the tyrosine units have reacted, which can be confirmed by amino acid analysis. The reaction between flame retardant and silk only occurs in the amorphous region of silk fibre, which is confirmed by X-ray diffraction analysis and amino acid analysis. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis show that the flame retardant causes silk fabrics to decompose below its ignition temperature (600°C) and formed carbonaceous residue or char when exposed to fire. The char behaves as a thermal barrier to fire, so silk fabrics show good flame retardancy. The treatment has a little effect on the whiteness of the silk fabrics and the tensile strength of treated silk fabrics slightly decreased; both effects are negligible. Copyright © 2006 John Wiley & Sons, Ltd. [source]


    3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors prevent the progression of renal dysfunction in Japanese hypertensive patients

    GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 3 2010
    Masanori Kuwabara
    Aim: The aim was to determine whether the use of statins prevents the progression of chronic kidney disease (CKD) in hypertensive patients. Methods: We retrospectively reviewed data obtained from hypertensive patients, and subjects with diabetes mellitus and those undergoing hemodialysis were excluded. At total of 227 patients were enrolled (83 men, mean age 73 years) and 90% of the patients were of CKD stage 2 or 3. The patients were divided into two groups: those treated with statins (n = 93) and those not treated with statins (n = 134). Renal function was evaluated by estimated glomerular filtration rate (eGFR). Results: The statin group and the non-statin group were similar in age, sex, blood pressure, follow-up period and prescriptions of antihypertensive medicines. The eGFR in the statin group increased from 62 ± 14 to 66 ± 15 (mL/min per 1.73 m2), whereas it decreased in the non-statin group from 69 ± 16 to 64 ± 18 (mL/min per 1.73 m2). The annual eGFR improved in the statin group (2.5 ± 6.6 mL/min per 1.73 m2/year), but decreased in the non-statin group (,3.3 ± 6.6 mL/min per 1.73 m2/year) (P < 0.001). When the patients were divided into two groups by low-density lipoprotein (LDL) cholesterol levels at the second evaluation, annual eGFR improved in the group of LDL to below 100 mg/dL (n = 99) (0.4 ± 7.2 mL/min per 1.73 m2/year), but decreased in the other group (n = 128) (,1.9 ± 7.0 mL/min per 1.73 m2/year) (P = 0.018). Conclusion: Lipid-lowering intervention with statins inhibits the progression of CKD in hypertensive patients. Geriatr Gerontol Int 2010; 10: 219,224. [source]


    An economic model of haemophilia in Mexico

    HAEMOPHILIA, Issue 1 2004
    C. Martínez-Murillo
    Summary., A model was developed to assess the lifetime costs and outcomes associated with haemophilia in Mexico. A retrospective chart review of 182 type A haemophiliacs was conducted for patients aged 0,34 years receiving one of three treatments: (i) cryoprecipitate at clinic; (ii) concentrate at home; or (iii) concentrate at clinic. Patients treated at home experienced 30% less joint damage, used 13,54% less factor VIII, had four times fewer clinic visits, and utilized half as many hospital days than those treated at a clinic. For cryoprecipitate at clinic patients, the annual incidence rates of HCV and HIV were calculated to be 3.6% and 1.4% respectively. The life expectancy for patients receiving cryoprecipitate and those receiving concentrate was estimated to be 49 years and 69 years respectively, with 58% of cryoprecipitate patients predicted to die of AIDS before age 69. Across the lifespan, the average annual cost of care was US$11 677 (MN$110 464) for cryoprecipitate at clinic patients, US$10 104 (M$95 580) for concentrate at home patients and US$18 819 (MN$178 027) for concentrate at clinic patients. Using a 5% discount rate, the incremental lifetime cost per year of life added for treatment with concentrate at home compared with cryoprecipitate at a clinic was US$738 (MN$6981). Rank order stability analysis demonstrated that the model was most sensitive to the cost of fVIII. These results indicate that treatment with concentrate at home compared with cryoprecipitate at a clinic substantially improves clinical outcomes at reduced annual cost levels. [source]