We define the target, mechanism, and structural basis of inhibition of bacterial RNA polymerase (RNAP) by the tetramic-acid antibiotic streptolydigin (Stl). Stl binds to a site adjacent to, but not overlapping, the RNAP active center and stabilizes an RNAP-active-center conformational state with a straight bridge helix. The results provide direct support for the proposals that alternative straight-bridge-helix and bent-bridge-helix RNAP-active-center conformations exist, and that cycling between straight-bridge-helix and bent-bridge-helix RNAP-active-center conformations is required for RNAP function. The results set bounds on models for RNAP function and suggest strategies for design of novel antibacterial agents.
Semaphorins are a large family of transmembrane proteins. The gene for SEMA4A encodes a transmembrane protein comprising 760 amino acids. To investigate its association with human retinal degeneration, mutation screening of the SEMA4A gene was carried out on 190 unrelated patients suffering from a variety of eye diseases. We report the first observation of the involvement of SEMA4A gene mutations causing retinitis pigmentosa (RP) and cone rod dystrophy (CRD). We screened the DNA of 135 patients with RP, 25 patients with CRD, and 30 with LCA using SSCP and direct DNA sequencing for mutations in the SEMA4A gene. Two mutations, p.D345H and p.F350C, were observed only in affected patients; they were not observed in any of the normal members or the 100 control subjects. Both mutations identified occur in the conserved semaphorin domain. Multiple sequence alignments using Clustal analysis showed that R713Q is a conserved substitution and D345H is a semi‐conserved substitution. We conclude that these mutations are a cause of various retinal degenerations.
SEMA4A; retinal degeneration; retinitis pigmentosa; cone rod dystrophy
Background: The response rates and duration of peginterferon alpha (PEG-IFN-α) and ribavirin combination therapy in chronic hepatitis C genotype 4, the prevalent genotype in the Middle East and Africa, are poorly documented.
Aims: To compare the efficacy and safety of 24, 36, or 48 weeks of PEG-IFN-α-2b and ribavirin therapy in chronic hepatitis C genotype 4.
Methods: In this prospective, randomised, double blind study, 287 patients with chronic hepatitis C genotype 4 were randomly assigned to PEG-IFN-α-2b (1.5 μg/kg) once weekly plus daily ribavirin (1000–1200 mg) for 24 weeks (group A, n = 95), 36 weeks (group B, n = 96), or 48 weeks (group C, n = 96) and followed for 48 weeks after completion of treatment. Early viral kinetics and histopathological evaluation of pre- and post treatment liver biopsies were performed. The primary end point was viral clearance 48 weeks after completion of treatment.
Results: Sustained virological response was achieved in 29%, 66%, and 69% of patients treated with PEG-IFN-α-2b and ribavirin for 24, 36, and 48 weeks, respectively, by intention to treat analysis. No statistically significant difference in sustained virological response rates was detected between 36 and 48 weeks of therapy (p = 0.3). Subjects with sustained virological response showed greater antiviral efficacy (ɛ) and rapid viral load decline from baseline to treatment week 4 compared with non-responders and improvement in liver histology. The incidence of adverse events was higher in the group treated for 48 weeks.
Conclusion: PEG-IFN-α-2b and ribavirin for 36 or 48 weeks was more effective in the treatment of chronic hepatitis C genotype 4 than treatment for 24 weeks. Thirty six week therapy was well tolerated and produced sustained virological and histological response rates similar to the 48 week regimen.
hepatitis C; peginterferon α-2b; ribavirin; sustained virological response
We conducted a systematic review to examine the effectiveness of educational interventions in increasing mammography screening among low-income women.
Bibliographic databases, including MEDLINE, The Cochrane Central Register of Controlled Trials, The Cochrane Database of Systematic Reviews, and the ISI Web of Science, were searched for relevant articles.
Study Inclusion and Exclusion Criteria
Randomized, community-based trials targeting low-income women and published between January 1980 and March 2003 were included.
The search yielded 242 studies; 24 met all inclusion criteria.
Three studies used mammography vans, three used low-cost vouchers or provided free mammograms, three used home visits, one used community education alone, one provided referrals, five incorporated multiple intervention strategies, two used phone calls, one used videos and print material, and five used primarily print material.
Of nine studies that reduced barriers to care via mammography vans, cost vouchers, or home visits, eight showed statistically significant increases in mammography screening. Seven of the eight studies that used peer educators had significant increases in screening, as did four of the five studies that used multiple (intervention) components.
Interventions that used peer educators, incorporated multiple intervention strategies, or provided easy access via vans, cost vouchers, or home visits were effective in increasing screenings. Mailed letter or telephone reminders were not effective in trials involving low-income women, which is contrary to findings from middle/upper-income studies.
Mammography Screening; Effective Interventions; Prevention Research; Manuscript format: literature review; Primary variables: behavioral; Setting: local community; Health focus: medical self-care; Strategy: skill building/behavior change; Target population: adults and seniors; Target population circumstances: education/income level, geographic location, race/ethnicity
This study examines the current prevalence of cigarette smoking and the number of cigarettes smoked in a community-based sample of 1021 low-income African-American men and women.
Participants were selected using a two-stage, area probability sample design. Data were collected in 2002–2003 in face-to-face interviews and analyzed in 2005. All data and analyses were weighted to account for the complex sampling design.
Fifty-nine percent of men and 41% of women were current smokers, with younger individuals apparently initiating smoking at an earlier age than older individuals.
The high prevalence of cigarette use provides further evidence that the excess burden of tobacco-related disease among low-income African-American families may be on the rise. This is of great concern, and if confirmed by further research, indicates an urgent need for preventive intervention.
Low-income African American children experience high rates of dental caries compared to the general population. Knowledgeable and efficacious caregivers can play an important role in caries prevention. This study developed and evaluated four brief measures reflecting mothers’ potentially modifiable cognitions associated with African American children’s oral health: (1) knowledge about appropriate bottle use (KBU); (2) children’s oral hygiene (KCOH); (3) oral health-related fatalism (OHF); and (4) oral health-related self-efficacy (OHSE).
Questions were selected based on reviews of the health promotion and oral health literature, with input from low income African American caregivers of young children. Reliability and validity were evaluated using survey and dental examination data from 719 low-income African American mothers and their children ages 1–5 years.
Alpha reliabilities ranged from .76 – .91. KCOH was significantly associated with mothers’ oral health perceptions and children’s caries status. OHSE was significantly positively correlated with children’s brushing frequency and with mothers’ subjective perceptions of children’s oral health, which was in turn significantly associated with children’s caries status.
Results support the reliability and validity of the new measures. If confirmed by further research, these measures can be used to develop tailored educational and cognitive-behavioral interventions to reduce oral health disparities.
A study on the response of the external anal sphincter (EAS) to the passage of urine through the urethra during micturition could not be found in the literature. We investigated the hypothesis that urine passage through the urethra effects EAS contraction to guard against possible flatus or stool leakage during micturition.
The study was performed in 23 healthy volunteers (age, 38.6 ± 10.8 [SD] years; 14 men and 9 women). The EAS electromyogram (EMG) was performed during micturition by surface electrodes applied to the EAS. Also, the EAS EMG response to urethral stimulation by a catheter-mounted electrode was registered. The test was repeated after individual anesthetization of the EAS and urethra.
The EAS EMG recorded a significant increase (P < 0.01) during micturition and on urethral stimulation at the bladder neck. Stimulation of the prostatic, membranous, or penile urethra produced no significant change in the EAS EMG. Urethral stimulation after individual EAS and urethral anesthetization did not cause any changes in the EAS EMG.
Urine passing through the urethra or urethral stimulation at the vesical neck produced an increase in the EAS EMG, which presumably denotes EAS contraction, which seems to guard against flatus or fecal leakage during micturition. EAS contraction on urethral stimulation is suggested to be mediated through a urethro–anal reflex. Further studies on this issue may potentially prove the diagnostic significance of this reflex in micturition and defecation disorders.
Electromyography; Sphincter reflex; Flatus; Stools; Urethra; Defecation; Micturition
To determine the prevalence of cases and episodes of needlestick injury among three groups of health care workers in the past one-year, the level of knowledge on blood-borne diseases and universal precautions and the practice of universal precautions. Other factors associated with the occurrence of needlestick injuries and the reporting of needlestick injuries were also analysed.
A cross-sectional study was conducted in May 2003 to study the needlestick injuries among 285 health care workers (doctors, nurses, medical students) in a public teaching hospital in Negeri Sembilan, Malaysia.
The prevalence of needlestick injuries among the respondents was 24.6% involving 71 cases i.e. 48.0% among doctors, 22.4% among medical students, and 18.7% among nurses and the difference was statistically significant (p<0.001). There were a total of 174 episodes of needlestick injury. Prevalence of episode of needlestick injuries was highest among doctors (146%), followed by nurses (50.7%) and medical students (29.4%). Cases of needlestick injuries attained lower scores on practice of universal precautions compared to non-cases (p<0.001). About 59% of cases of needlestick injury did not report their injuries.
The study showed that needlestick injuries pose a high risk to health care workers and it is underreported most of the time. Many needlestick injuries can be prevented by strictly following the practice of universal precautions.
needlestick injury; health care workers; prevalence; underreporting; Malaysia
It has been acknowledged that religious and complementary therapies are commonly used among South Asian communities in the UK. However, little is known about their religious beliefs in relation to epilepsy and the type of South Asian therapies that they use to treat the condition.
To explore the influences of spiritual and religious beliefs on explanation of the cause of epilepsy, and the choice of treatment in people of South Asian origin who have epilepsy.
Design of study
Qualitative study using interviews with patients, carers, health professionals, and focus groups of people from minority ethnic communities.
Bradford and Leeds.
Semi-structured individual interviews with 20 Muslims, six Sikhs, and four Hindus with epilepsy; 16 nominated carers (family members, friends); 10 health professionals (specialist GPs, neurologists, specialists nurses, social workers, community GPs); and two focus groups with a total of 16 South Asians without epilepsy.
It was found that over half of responders attributed their illness to fate and the will of God, or as punishment for sins of a past life. Some patients had experienced prejudice from people who believed that their epilepsy was contagious. A strong network of traditional healers was found, providing a parallel system of health care in the UK and on the Indian subcontinent. People turned to religiospiritual treatments in desperation for a cure, often under the influence of their families after the perceived failure of Western medicine. Such treatments were viewed as complementary rather than as an alternative to Western medication. Younger people in particular expressed considerable scepticism about the effectiveness of these traditional South Asian treatments.
In this study's South Asian sample, patients commonly turned to traditional healers in search of better health. Health professionals should be aware of the belief systems of these patients and understand the types of treatments in common use. Although these treatments might potentially compete with Western health care, they are used as an adjunct rather than a substitute. Patients have a ‘healthy’ scepticism about the effectiveness of such treatments, and adherence to medical therapy does not appear to be affected.
beliefs; epilepsy; medicine, traditional; Southern Asia; spirituality
The proteasome inhibitor Velcade (bortezomib/PS-341) has been shown to block the targeted proteolytic degradation of short-lived proteins that are involved in cell maintenance, growth, division, and death, advocating the use of proteasomal inhibitors as therapeutic agents. Although many studies focused on the use of one proteasomal inhibitor for therapy, we hypothesized that the combination of proteasome inhibitors Lactacystin (AG Scientific, Inc., San Diego, CA) and MG132 (Biomol International, Plymouth Meeting, PA) may be more effective in inducing apoptosis. Additionally, this regimen would enable the use of sublethal doses of individual drugs, thus reducing adverse effects. Results indicate a significant increase in apoptosis when LNCaP prostate cancer cells were treated with increasing levels of Lactacystin, MG132, or a combination of sublethal doses of these two inhibitors. Furthermore, induction in apoptosis coincided with a significant loss of IKKα, IKKβ, and IKKγ proteins and NFκB activity. In addition to describing effective therapeutic agents, we provide a model system to facilitate the investigation of the mechanism of action of these drugs and their effects on the IKK-NFκB axis.
Prostate; apoptosis; proteasomal inhibitors; Lactacystin; MG132
CHROMagar Candida medium is used for the isolation and identification of Candida species, but it does not differentiate Candida albicans from Candida dubliniensis. This differentiation can be achieved by using Pal's agar, which cannot be used in primary isolation. We have combined both media to obtain a new medium that can be used for the isolation and identification of C. dubliniensis in primary cultures.
Thrombin generation assay was developed several years ago to mimic physiological coagulation mechanisms but it had important limitations. Thrombogram-Thrombinoscope assay using a fluorogenic substrate, allows obtaining thrombin generation curves in non-defibrinated platelet rich plasma (PRP) in a fully automated manner.
We standardised the methodology of Thrombogram-Thrombinoscope and we evaluated the precision of thrombin generation parameters (lag-time, maximum concentration of thrombin [Cmax], time required to reach Cmax [Tmax] and endogenous thrombin potential ETP) using different concentrations of recombinant human tissue factor, platelets or phospholipids. Normal values of thrombin generation assay were established in optimal experimental conditions.
In the presence of low TF concentrations (final dilution of thromboplastin in plasma: 1/1000–1/2000) the Thrombogram assay showed intra-assay and inter-assay coefficients of variation lower than 9%. Thrombin generation parameters showed an important inter-individual variability and the coefficients of variation ranged from 18% to 50%. In PRP the lag-time, Cmax and Tmax but not the ETP, were influenced by TF concentration. Thrombin generation parameters were not influenced by variations of platelet concentration from 50 × 109/l to 400 × 109/l. The addition of synthetic procoagulant phospholipids in PPP strongly influenced all the parameters of thrombogram. For all the parameters of thrombogram a threshold effect was observed in the presence of phspholipid concentrations equal or higher to 4 μM. In frozen-thawed PRP the lag-time and the Tmax were significantly reduced and the Cmax was increased compared to the fresh PRP, but the ETP, the intra assay and the inter-assay coefficients of variation were similar in both test-systems.
Thrombogram-Thrombinoscope assay performed in fresh or in frozen-thawed PRP has an acceptable precision, with low inter-assay and intra-assay coefficient of variations. The concentration of TF is determinant for the normal values of the studied parameters of thrombin generation. When the assay is performed in PPP, thrombin generation parameters are influenced by the concentration of procoagulant synthetic phospholipids. The optimal experimental conditions were obtained in the presence of 1/1000 final dilution of thromboplastin, a platelet count higher than 50 × 109/l and a synthetic phospholipid concentration higher than 4 μM.
Thrombin generation; Thrombinoscope; endogenous thrombin potential; thrombin; platelets; tissue factor
In India, there is a paucity of trained professionals to execute psychosocial interventions. Families are thus assigned the role of primary caretakers of individuals with chronic mental illness.
To assess the perceived benefits and difficulties of group meetings among caregivers of persons with schizophrenia and bipolar mood disorders, and to evaluate the utilization pattern of general hospital psychiatric unit (GHPU) services by caregivers who regularly attend such group meetings.
Persons with schizophrenia and those with bipolar mood disorders with associated psychosocial problems and on maintenance medication were identified at the Psychiatric Rehabilitation Unit of the Department of Psychiatry, Father Muller Medical College. Significant caregivers of the identified patients were informed about the group meeting. Group meetings were conducted for about 45 minutes once a month for caregivers of patients with schizophrenia and bipolar mood disorders. Data regarding the psychosocial aspects of caregivers were collected before entry to the meeting and after 17 months of their participation. Participants who attended the meetings irregularly were excluded from the study.
The group meetings led to effective monitoring of the functioning of individuals, a reduction in the subjective family burden and family distress, a better support system with adequate coping skills and good compliance with treatment programmes.
Conducting regular group meetings for a homogeneous population at a GHPU is feasible and beneficial.
Caretakers'group meeting; schizophrenia; bipolar mood disorders
The elderly consume many medications including traditional medicines. In 1986, it was found that 29% of elderly took traditional medicines although in 1996, the National Health Morbidity survey reported a 2.3% prevalence. However, studies from other countries showed much higher percentages. The Ministry of Health in Malaysia is concerned that some of these preparations maybe contaminated with steroids, antihistamines, hormones and other poisons. The aims of the study were to determine a). the health seeking behaviour of elderly Malays living in rural areas, b). the utilization of both modern and traditional medicines and c). the steroid content of the traditional medicines used. Methodology included interviews using structured questionnaires of elderly Malays living in rural areas of Kelantan, aged above 60 years. Samples of traditional medications collected were sent to the Pharmacology Department, School of Medical Sciences, Universiti Sains Malaysia, for steroid content analysis using Thin Layer Chromatography. A total of 599 elderly respondents were interviewed comprising 62.4% females and 37.6% males. The 60–69 years cohort group made up 48.7%, followed by 70–79 years at 36.1% and the remainder 15.2% were more than 80 years. There were 82% of elderly taking medicines. The trends of utilization of modern and traditional medicine in the last two weeks among elderly were 59.3% and 40.9% respectively. The utilization of traditional medicine by rural elderly Malays was therefore much higher than that reported in the previous study and nearly similar to that of France and Australian studies. There were 102 samples of traditional medications collected and analysed for steroid content. Results showed that 27.5% were positive for prednisolone, 34.3% positive for unknown steroids (a total of 61.8%) and 38.2% were negative for both steroids. The present study therefore once again confirmed the high usage of traditional medicines where some of which are contaminated with steroids.
Rural elderly; traditional medicines; steroids; prednisolone
Sarcoidosis is a chronic, systemic inflammatory disease of unknown etiology, characterized by noncaseating granulomatous infiltration of any organ. Sickle cell anemia (SCA) is the homozygoid form of sickle cell disease (SCD), which includes a group of genetic disorders characterized by production of an abnormal hemoglobin S (HbS). There are a few case reports with coexistence of sarcoidosis and SCA. We reported a 47-year-old female with SCA and sarcoidosis.
Senescence, the molecular program that limits the finite proliferative potential of a cell, acts as an important barrier to protect the body from cancer. Techniques for measuring transcriptome changes and for modulating their expression suggest that it may be possible to dissect the transcriptional networks underlying complex cellular processes. HMF3A cells are conditionally immortalized human mammary fibroblasts that can be induced to undergo coordinated senescence. Here, we used these cells in conjunction with microarrays, RNA interference, and in silico promoter analysis to promote the dissection of the transcriptional networks responsible for regulating cellular senescence. We first identified changes in the transcriptome when HMF3A cells undergo senescence and then compared them with those observed upon replicative senescence in primary human mammary fibroblasts. In addition to DUSP1 and known p53 and E2F targets, a number of genes such as PHLDA1, NR4A3, and a novel splice variant of STAC were implicated in senescence. Their role in senescence was then analyzed by RNA silencing followed by microarray analysis. In silico promoter analysis of all differential genes predicted that nuclear factor-κB and C/EBP transcription factors are activated upon senescence, and we confirmed this by electrophoretic mobility shift assay. The results suggest a putative signaling network for cellular senescence.
A 65-year-old man underwent coronary artery bypass graft surgery at our tertiary care hospital. Perioperatively, he was transfused with four units of nonirradiated whole blood from first-degree relatives and discharged from the hospital at postoperative day seven. He presented six days later with fever, skin rash, elevated liver enzymes, and progressive pancytopenia. Elevated bilirubin levels and diarrhea were added to the clinical picture over the following days. Clinical findings and results of a skin biopsy specimen were consistent with transfusion-associated graft-versus-host disease. The patient died 20 days after transfusion.
The etiological agent most commonly associated with bacillary dysentery is Shigella. As part of its mandate, the Bacteriology and Enteric Disease Program of Health Canada identifies and serotypes unusual isolates of Shigella received from provincial laboratories of public health. In this report, six unusual isolates from three provinces were analyzed biochemically and serologically using slide and tube agglutinations and molecularly using standard pulsed-filed gel electrophoresis (PFGE), PCR, and PCR-restriction fragment length polymorphism (RFLP) techniques. All six isolates were identical. PFGE analysis grouped these strains; biochemically, they were mannitol negative and consistent with the profile of Shigella. Serologically, these strains produced weak reactions in Shigella dysenteriae serovars 4 and 16 and Escherichia coli O159 and O173 antisera. Molecular serotyping by PCR-RFLP of the rfb gene produced an S. dysenteriae serovar 2/E. coli O112ac pattern. They were positive by PCR for ipaH and ial enteroinvasive genes but negative for all other genes tested. Antiserum was prepared from one of the isolates and tested against Shigella and E. coli reference strains as well as the other isolates. The antiserum reacted with the five remaining isolates and showed cross-reactivity with S. dysenteriae serovars 1, 4, and 16; Shigella flexneri type 3; and E. coli O118, O159, O168, O172, and O173 antigens. Absorbing the sera with E. coli O159 and S. dysenteriae serovar 4 antigen removed all cross-reactions and only slightly reduced the homologous titer. Based on biochemical, molecular, and complete serological analysis, we propose that these six isolates represent a new provisional serovar of S. dysenteriae, type strain BEDP 02-5104.
Although the interconversion between C4 and C3 compounds has an
important role in overall metabolism, limited information is available
on the properties and regulation of enzymes acting on these
metabolites in hyperthermophilic archaea. Malic enzyme is one of the
enzymes involved in this interconversion, catalyzing the oxidative
decarboxylation of malate to pyruvate as well as the reductive
carboxylation coupled with NAD(P)H. This study focused on the
enzymatic properties and expression profile of an uncharacterized
homolog of malic enzyme identified in the genome of a heterotrophic,
kodakaraensis KOD1 (Tk-Mae). The amino acid
sequence of Tk-Mae was 52–58% identical to
those of malic enzymes from bacteria, whereas the similarities to the
eukaryotic homologs were lower. Several catalytically important
regions and residues were conserved in the primary structure of
Tk-Mae. The recombinant protein, which formed a
homodimer, exhibited thermostable malic enzyme activity with strict
divalent cation dependency. The enzyme preferred NADP+
rather than NAD+, but did not catalyze the decarboxylation
of oxaloacetate, unlike the usual NADP-dependent malic enzymes. The
apparent Michaelis constant (Km) of
Tk-Mae for malate (16.9 mM) was much larger than
those of known enzymes, leading to no strong preference for the
reaction direction. Transcription of the gene encoding
Tk-Mae and intracellular malic enzyme activity in
T. kodakaraensis were constitutively weak, regardless
of the growth substrates. Possible roles of Tk-Mae
are discussed based on these results and the metabolic pathways of
T. kodakaraensis deduced from the genome sequence.
carbon metabolism; hyperthermophile; malate; pyruvate; tricarboxylic acid cycle
Untreated patent ductus arteriosus carries a higher risk in adults than in children, especially when the defect is large (>4.0 mm in diameter), short, or friable. Therefore, various technical precautions have been suggested for application during surgical closure of a patent ductus arteriosus in an adult. We report the case of a 47-year-old woman with a patent ductus arteriosus who underwent transpulmonary surgical closure of the ductus under hypothermic total circulatory arrest. We discuss the technique in light of the current English-language medical literature.
Adult; cardiopulmonary bypass; circulatory arrest; congenital heart disease; ductus arteriosus, patent/surgery; female
In open-heart surgery, sternal wound infection after median sternotomy is a critical complication. The intracutaneous suture is conventionally used in closing sternal incisions. In this prospective, randomized, controlled clinical trial, intracutaneous and transcutaneous suture techniques for closing the sternum were compared with respect to postoperative sternal wound infections and cosmetic results.
In this study, we included 100 patients who had undergone open-heart surgery. Skin wounds were closed with intracutaneous suture in 50 patients and with transcutaneous suture in the remaining 50. Superficial or deep sternal infections that developed within 6 postoperative weeks were evaluated.
Cosmetic results were similar in the 2 groups. Deep wound infections were not observed in either group. Superficial infection of postoperative sternal wounds occurred at rates of 2% (n = 1) and 16% (n = 8) for transcutaneous and intracutaneous techniques, respectively (P = 0.016). One patient in the transcutaneous group and 6 patients in the intracutaneous group who developed superficial sternal infections were diabetic.
Although the use of the transcutaneous suture technique in closing sternal incisions of cardiac surgery patients provided no cosmetic improvement, it decreased the risk of superficial sternal infection and reduced the length of postoperative hospital stay, particularly in diabetic patients.
Comparative study; diabetes complications; drainage; mediastinitis/etiology; postoperative complications/prevention & control; prospective studies; risk factors; sternum/surgery; suppuration; surgical wound dehiscence; surgical wound infection/prevention & control; suture techniques
Hypophosphatasia is a clinically heterogeneous inheritable disorder characterized by defective bone mineralization and the deficiency of serum and tissue liver/bone/kidney alkaline phosphatase activities. Due to the mineralization defect of the bones, various skeletal findings can be radiologically observed in hypophosphatasia. Bowing and Bowdler spurs of long bones are the characteristic findings. The Bowdler spurs reported on in the previous pertinent literature were observed in the perinatal aged patients and these lesions have rarely involved adolescents. We herein report on a 14-year-old girl with fibular Bowdler spurs.
Hypophosphatasia; Adolescent; Fibular Bowdler spurs