The Evolving Theory of Evolutionary Radiations.

Evolutionary radiations have intrigued biologists for more than 100 years, and our understanding of the patterns and processes associated with these radiations continues to grow and evolve. Recently it has been recognized that there are many different types of evolutionary radiation beyond the well-studied adaptive radiations. We focus here on multifarious types of evolutionary radiations, paying special attention to the abiotic factors that might trigger diversification in clades. We integrate concepts such as exaptation, species selection, coevolution, and the turnover-pulse hypothesis (TPH) into the theoretical framework of evolutionary radiations. We also discuss other phenomena that are related to, but distinct from, evolutionary radiations that have relevance for evolutionary biology.

General or Spinal Anaesthetic for Vaginal Surgery in Pelvic Floor Disorders (GOSSIP): a feasibility randomised controlled trial.

INTRODUCTION AND HYPOTHESIS: Spinal anaesthesia (SA) and general anaesthesia (GA) are widely used techniques for vaginal surgery for pelvic floor disorders with inconclusive evidence of the superiority of either. We conducted a randomised controlled trial (RCT) to assess the feasibility of a full scale RCT aiming to examine the effect of anaesthetic mode for vaginal surgery on operative, patient reported and length of hospital stay (LOHS) outcomes. METHODS: Patients undergoing vaginal surgery, recruited through a urogynaecology service in a University teaching hospital, were randomised to receive either GA or SA. Patients were followed up for 12 weeks postoperatively. Pain was measured on a visual analogue scale; nausea was assessed with a four-point verbal rating scale. Patient's subjective perception of treatment outcome, quality of life (QoL) and functional outcomes were assessed using the International Consultation on Incontinence Modular Questionnaire (ICIQ) on vaginal symptoms and the SF-36 questionnaire. RESULTS: Sixty women were randomised, 29 to GA and 31 to SA. The groups were similar in terms of age and type of vaginal surgery performed. No statistically significant differences were noted between the groups with regard to pain, nausea, quality of life (QoL), functional outcomes as well as length of stay in the postoperative recovery room, use of analgesia postoperatively and LOHS. CONCLUSION: This study has demonstrated that a full RCT is feasible and should focus on the length of hospital stay in a subgroup of patients undergoing vaginal surgery where SA may help to facilitate enhanced recovery or day surgery.

Developing Objective Metrics for Unit Staffing (DOMUS) study.

OBJECTIVE: Safe midwifery staffing levels on delivery suites is a priority area for any maternity service. Escalation policies are tools that provide an operational response to emergency pressures. The aim of this study was to assess the feasibility of using a scoring system to contemporaneously assess the required staffing level based on demand and use this to determine delivery suite escalation level and utilise the information generated regarding clinical activity (Demand) and staffing levels (Capacity) to generate unit-specific calculation for the actual number of midwifery staff required. SETTING: A maternity unit of a university-affiliated tertiary referral hospital. DESIGN: Over a 12-month period, specifically designed scoring sheets were completed by delivery suite shift co-ordinators four times a day (04:00, 10:00, 16:00 and 22:00). Based on the dependency score (Demand) and the number of midwifery staff available (Capacity), an escalation level was determined for each shift. The 80th centile of the demand was used to determine optimal capacity. RESULTS: A total of 1160 scoring sheets were completed. Average staff number throughout the year on any shift was 7 (range 3-11). Average dependency score was 7 (range 1-14). The 80th centile for demand was calculated to be 11. CONCLUSIONS: This study stresses the importance and usefulness of a simple tool that can be used to determine the level of escalation on delivery suite based on an objective scoring system and can also be used to determine the appropriate staffing on delivery suite.

Synchronous of breast and vulvar Paget's disease: a case report.

BACKGROUND: Synchronous Paget's disease of breast and vulva is extremely rare and has only been reported in the literature in one other case. CASE: A 58-year-old postmenopausal woman was found to have crusting, bleeding, and discharge from left nipple, as well as vulvar pruritis at the same time. Biopsy of breast lesion demonstrated Paget's disease with an underlying foci of ductal carcinoma in-situ that required total mastectomy of left breast with sentinel node biopsy and breast reconstruction. For vulvar symptoms, the patient was initially diagnosed with dermatitis and topical ointment was prescribed. However, her symptoms persisted for the next several months, and she underwent vulvar biopsy that demonstrated Paget's disease. She underwent partial vulvectomy. Multiple episodes of recurrent vulvar Paget's disease were noted in the postoperative course that medical therapy with Imiquimod and a second partial vulvectomy was performed. CONCLUSION: Synchronous of breast and vulvar Paget's disease is presented. There was a delay in diagnosing vulvar Paget's disease in this experienced case. While coincidence of breast and vulvar Paget's disease is likely, ectopic mammary tissue in vulvar as well as secondary metastasis from a focal lesion of breast Paget's disease needs to be carefully evaluated whenever the patient complains of vulvar symptoms in the setting of breast Paget's disease.

Prioritisation of teaching topics in obstetrics and gynaecology: a Delphi survey of postgraduate trainees.

Topics for theoretical teaching during the obstetrics and gynaecology specialty training programme are often chosen by tutors, with little input from the trainees. However, it is important to actively involve adults in their learning process to maintain their learning ownership and motivation. The Delphi methodology is a generic social science technique used to aggregate views and opinions of experts, the community and service users. In this study, we conducted a two generational Delphi study to achieve consensus between a group of trainees in obstetrics and gynaecology, regarding what they considered important topics for inclusion in their protected teaching programme. A total of 25 trainees from one deanery, participated in this study. We were able to produce a list of 26 topics in obstetrics and 30 in gynaecology, prioritised according to their importance for inclusion in the specialty protected teaching programme, as viewed by these trainees.

Surgical complications of segmental Le Fort I osteotomy.

Segmental maxillary osteotomy is a useful adjunct in orthognathic surgery for the correction of vertical and transverse maxillary deformities, but we know of few published reports that document complications. We evaluated the complication rates associated with segmental maxillary surgery in our unit by retrospective review of medical records, radiographs, and study models of 85 consecutive patients (mean age 23.3 years, range 14-51; male:female ratio 1:2) treated from 1995 to 2009. Types of deformity were anterior open bite (n=30, 35%), transverse maxillary deficiency (n=24, 28%), anterior open bite with transverse maxillary deficiency (n=28, 33%), and anterior vertical maxillary excess (n=3, 4%). There were 70 tripartite (82%), 13 bipartite (15%), and two quadripartite (2%) maxillas. Twenty-one patients (25%) had bone grafts. Fixation was done using titanium miniplates in 80 patients (94%), and titanium miniplates and resorbable plates in five (6%). The overall complication rate was 27%. Three patients (4%) had devitalisation of teeth, three (4%) developed minor periodontal defects, and one had tooth loss. Eight patients (9%) had plates removed, and two patients developed persistent postoperative palatal fistula. There was no segmental loss of bone or teeth. Our results show that complications in this cohort were relatively low, and that segmental maxillary surgery is safe as an adjunct in carefully selected cases.

Effects of changes to the stable environment on the exhalation of ethane, carbon monoxide and hydrogen peroxide by horses with respiratory inflammation.

The aim of this study was to assess the effects of changes to the stable environment on exhaled markers of respiratory inflammation in six horses with clinical histories of recurrent airway obstruction. The horses were maintained for two weeks under conventional stable management (straw bedding and hay) and for two weeks on a reduced-dust regimen (paper bedding and ensiled grass), in a crossover study design. Exhaled ethane and carbon monoxide (CO) and exhaled breath condensate hydrogen peroxide (H(2)O(2)) were measured every three days under each regimen. The presence of clinical signs of airway inflammation (nasal discharge and cough) was monitored daily. The reduced-dust regimen was associated with fewer clinical signs of airway inflammation than the conventional regimen. Exhaled ethane and CO were significantly lower on the reduced-dust regimen and these markers were correlated with clinical signs of respiratory inflammation, but exhaled H(2)O(2) was not affected by the management regimen.

Noonan syndrome with giant cell lesions.

Noonan syndrome is characterised by short stature, unusual facies, congenital heart disease, chest deformity and mild mental retardation. It may be sporadic or inherited as an autosomal dominant trait and occurs between one in 1000-2500. Cherubism is a giant cell lesion of the jaws thought to be transmitted as an autosomal dominant trait. It is usually recognised by age two to four years, follows a variable course, and is not known to be related to other genetic disorders. The purpose of this article is to report a case of multiple giant cell lesions of the mandible that occurred in a patient with phenotypic features of Noonan syndrome. The emerging relationship between these cherubism-like findings and Noonan syndrome will be discussed.

A leucine-supplemented diet improved protein content of skeletal muscle in young tumor-bearing rats

Cancer cachexia induces host protein wastage but the mechanisms are poorly understood. Branched-chain amino acids play a regulatory role in the modulation of both protein synthesis and degradation in host tissues. Leucine, an important amino acid in skeletal muscle, is higher oxidized in tumor-bearing animals. A leucine-supplemented diet was used to analyze the effects of Walker 256 tumor growth on body composition in young weanling Wistar rats divided into two main dietary groups: normal diet (N, 18 percent protein) and leucine-rich diet (L, 15 percent protein plus 3 percent leucine), which were further subdivided into control (N or L) or tumor-bearing (W or LW) subgroups. After 12 days, the animals were sacrificed and their carcass analyzed. The tumor-bearing groups showed a decrease in body weight and fat content. Lean carcass mass was lower in the W and LW groups (W = 19.9 ± 0.6, LW = 23.1 ± 1.0 g vs N = 29.4 ± 1.3, L = 28.1 ± 1.9 g, P < 0.05). Tumor weight was similar in both tumor-bearing groups fed either diet. Western blot analysis showed that myosin protein content in gastrocnemius muscle was reduced in tumor-bearing animals (W = 0.234 ± 0.033 vs LW = 0.598 ± 0.036, N = 0.623 ± 0.062, L = 0.697 ± 0.065 arbitrary intensity, P < 0.05). Despite accelerated tumor growth, LW animals exhibited a smaller reduction in lean carcass mass and muscle myosin maintenance, suggesting that excess leucine in the diet could counteract, at least in part, the high host protein wasting in weanling tumor-bearing rats.

A leucine-supplemented diet improved protein content of skeletal muscle in young tumor-bearing rats.

Cancer cachexia induces host protein wastage but the mechanisms are poorly understood. Branched-chain amino acids play a regulatory role in the modulation of both protein synthesis and degradation in host tissues. Leucine, an important amino acid in skeletal muscle, is higher oxidized in tumor-bearing animals. A leucine-supplemented diet was used to analyze the effects of Walker 256 tumor growth on body composition in young weanling Wistar rats divided into two main dietary groups: normal diet (N, 18% protein) and leucine-rich diet (L, 15% protein plus 3% leucine), which were further subdivided into control (N or L) or tumor-bearing (W or LW) subgroups. After 12 days, the animals were sacrificed and their carcass analyzed. The tumor-bearing groups showed a decrease in body weight and fat content. Lean carcass mass was lower in the W and LW groups (W = 19.9 0.6, LW = 23.1 1.0 g vs N = 29.4 1.3, L = 28.1 1.9 g, P < 0.05). Tumor weight was similar in both tumor-bearing groups fed either diet. Western blot analysis showed that myosin protein content in gastrocnemius muscle was reduced in tumor-bearing animals (W = 0.234 0.033 vs LW = 0.598 0.036, N = 0.623 0.062, L = 0.697 0.065 arbitrary intensity, P < 0.05). Despite accelerated tumor growth, LW animals exhibited a smaller reduction in lean carcass mass and muscle myosin maintenance, suggesting that excess leucine in the diet could counteract, at least in part, the high host protein wasting in weanling tumor-bearing rats.

Development of an in-vitro model system to investigate the mechanism of muscle protein catabolism induced by proteolysis-inducing factor.

The mechanism of muscle protein catabolism induced by proteolysis-inducing factor, produced by cachexia-inducing murine and human tumours has been studied in vitro using C(2)C(12) myoblasts and myotubes. In both myoblasts and myotubes protein degradation was enhanced by proteolysis-inducing factor after 24 h incubation. In myoblasts this followed a bell-shaped dose-response curve with maximal effects at a proteolysis-inducing factor concentration between 2 and 4 nM, while in myotubes increased protein degradation was seen at all concentrations of proteolysis-inducing factor up to 10 nM, again with a maximum of 4 nM proteolysis-inducing factor. Protein degradation induced by proteolysis-inducing factor was completely attenuated in the presence of cycloheximide (1 microM), suggesting a requirement for new protein synthesis. In both myoblasts and myotubes protein degradation was accompanied by an increased expression of the alpha-type subunits of the 20S proteasome as well as functional activity of the proteasome, as determined by the 'chymotrypsin-like' enzyme activity. There was also an increased expression of the 19S regulatory complex as well as the ubiquitin-conjugating enzyme (E2(14k)), and in myotubes a decrease in myosin expression was seen with increasing concentrations of proteolysis-inducing factor. These results show that proteolysis-inducing factor co-ordinately upregulates both ubiquitin conjugation and proteasome activity in both myoblasts and myotubes and may play an important role in the muscle wasting seen in cancer cachexia.

Amelioration of CR-EAE with lisofylline: effects on mRNA levels of IL-12 and IFN-gamma in the CNS.

CR-EAE is a Th1-mediated inflammatory autoimmune demyelinating disease of the CNS and serves as a model of human multiple sclerosis. Our previous studies have shown the protective effect of orally administered lisofylline in the prevention of active and passively induced acute EAE. In our present studies we have examined the efficacy and mechanism of action of lisofylline on CR-EAE. Lisofylline decreased the number and severity of paralytic attacks in mice with relapsing EAE. The reduction of clinical disease correlated with decreased levels of mRNA levels of IFN-gamma but not of mRNA levels of IL-12. These studies suggest that lisofylline may be an effective therapeutic for established Th1 mediated autoimmune disease and that it acts by blocking IL-12R signaling and not IL-12 production in vivo.

Unusual T cell receptor phenotype V gene usage of gamma delta T cells in a line derived from the peripheral nerve of a patient with Guillain-Barré syndrome.

Guillain-Barré syndrome is considered to be an immune mediated disorder but the relative role of T cells and antibodies in its pathogenesis is unclear. As gut infection with Campylobacter jejuni is the most common antecedent infection it is possible that gut derived T lymphocytes might play a part in the development of the syndrome. The T cell receptor phenotype (TCR) of a nerve gamma delta T cell line obtained from a sural nerve biopsy taken from a patient with a demyelinating form of GBS was determined using polymerase chain reaction (PCR) and flow cytometry (FACS). This TCR was compared with the phenotype preferentially expressed in the peripheral blood of the same patient. The T cell nerve line was found to express V gamma 8/delta 1 which represents an unusual T cell subset normally found on lymphocytes resident in epithelial tissue such as the gut. The peripheral blood gamma delta T lymphocytes from the patient were of the V gamma 9/delta 2 subset, which is the phenotype predominantly expressed in the peripheral blood of healthy subjects. In conclusion, the presence of this unusual population of V gamma 8/delta 1(+) lymphocytes in nerve would be consistent with a pathogenetic role for gut associated lymphocytes in the pathogenesis of Guillain-Barré syndrome associated with C jejuni.

Transient changes in the synthesis of nitric oxide result in long-term as well as short-term changes in acetic acid-induced writhing in mice.

A single injection of nitric oxide (NO) synthase (NOS) inhibitors prevents the development of persistent hyperalgesia induced by various manipulations, suggesting that NO precipitates long-term changes in nociception. We examined the possibility that inhibition of NOS may also be sufficient to produce long-term decreases in nociceptive assays, such as writhing, that are known to be sensitive to the short-term effects of NOS inhibitors. We characterized short- and long-term effects of NOS inhibitors, N(omega)-nitro-L-arginine (L-NAME) or 7-nitro indazole (7-NI) injected intrathecally (i.t.) in mice on acetic acid-induced writhing. Doses of L-NAME that had no effect on hot plate or tail flick latencies inhibited writhing (0. 01-30 nmol) as well as spinal nNOS activity (5 and 100 nmol) when injected i.t. 60-90 min before testing. Anti-nociception was not mimicked by D-NAME but was prevented by co-administration with the NO precursor, L-arginine. Injection i.t. of 7-NI (30 min), a selective inhibitor of neuronal NOS (nNOS), inhibited NOS activity in the spinal cord and produced anti-nociception, confirming that writhing is sensitive to inhibition of nNOS. Although the acute action of both NOS inhibitors dissipated completely by 3-6 h, a delayed and prolonged inhibition of writhing was again observed 24 h after L-NAME (5-100 nmol), a time when spinal NOS activity was no longer inhibited by L-NAME (5 and 100 nmol) or 7-NI (25 nmol). This novel effect appears to be initiated by the transient inhibition of nNOS as delayed anti-nociception was mimicked by 7-NI at doses (10-100 nmol) that no longer inhibited spinal nNOS (25 nmol) at 24 h. Co-administration with L-arginine prevented the delayed (24 h) anti-nociceptive effects of L-NAME (30 nmol). L-Arginine (30 and 100 nmol) was without effect on nociception when administered alone 60 min or 24 h prior to testing. Together these data indicate that brief changes in the activity of nNOS induce both long- as well as short-term changes in nociception.