The Success and Evolution of a Urological "Boot Camp" for Newly Appointed UK Urology Registrars: Incorporating Simulation, Nontechnical Skills and Assessment.

BACKGROUND: Urological training has dramatically changed in recent years. Training durations are shorter and a drive toward consultant led care has reduced trainees experience. Within the UK, approximately 50 registrars annually embark on a 5-year Urology training programme, with variable levels of basic urological experience. OBJECTIVE: To describe a simulation programme aimed at delivering the knowledge and skills necessary to safely and effectively start working as a registrar in Urology by intensive training with a 1:1 faculty to delegate ratio. DESIGN, SETTING, AND PARTICIPANTS: Our course content mirrors the UK training syllabus for junior Urology registrars. We delivered 8 modules over a 4-day programme with a fifth day of assessments. Delegates level of urological knowledge, operative competency and confidence pre-, immediately post-training and at 3-months postcourse were assessed. Objective delegate and faculty feedback was also collected. Technical skills modules include; inguinoscrotal surgery, ureteroscopy, transurethral resection, urodynamics, and Botox administration as well as basic reconstructive and laparoscopic operative skills. "Nontechnical" skills included simulated ward round, out-patient, and emergency scenarios. RESULTS: Feedback from delegates and faculty members has been overwhelmingly positive. We have used this feedback to tailor the content of the course for following years. An increased knowledge level (based on mean examination scores [precourse 55.5%, postcourse 70.1%]) and operative competency was observed in all skills assessed (transurethral resection of the prostate, transurethral resection of bladder tumor, Ureteroscopy, laparoscopic skills, and instrument assembly). Operative confidence was increased immediately and at 3-months postcourse. CONCLUSIONS: Our "boot camp" course provides a realistic introduction and foundation to begin Urological practice. Being delivered at the beginning of the training scheme, prior to intensive patient exposure, registrars are in an optimum position to develop their newly acquired knowledge and skills to enhance training and intends to improve patient safety and satisfaction.

The autism-associated gene chromodomain helicase DNA-binding protein 8 (CHD8) regulates noncoding RNAs and autism-related genes.

Chromodomain helicase DNA-binding protein 8 (CHD8) was identified as a leading autism spectrum disorder (ASD) candidate gene by whole-exome sequencing and subsequent targeted-sequencing studies. De novo loss-of-function mutations were identified in 12 individuals with ASD and zero controls, accounting for a highly significant association. Small interfering RNA-mediated knockdown of CHD8 in human neural progenitor cells followed by RNA sequencing revealed that CHD8 insufficiency results in altered expression of 1715 genes, including both protein-coding and noncoding RNAs. Among the 10 most changed transcripts, 4 (40%) were noncoding RNAs. The transcriptional changes among protein-coding genes involved a highly interconnected network of genes that are enriched in neuronal development and in previously identified ASD candidate genes. These results suggest that CHD8 insufficiency may be a central hub in neuronal development and ASD risk.

The retention and recovery of amino acids from pork longissimus muscle following cooking to either 60°C or 75°C.

Samples of pork longissimus muscle (n=16) cooked to either 60°C or 75°C in a water bath for 90 min were assessed for amino acid composition. Recovery of protein in the cooked meat plus the cooking juice was >93% and was slightly higher at 60°C (P=0.031), but retention in the meat was only 89% and 82% for the lower and higher temperatures (P<0.0001). Individual amino acids varied in recovery and retention with retention being particularly low for taurine and histidine. The balance of indispensable amino acids was less than ideal, with leucine and valine being the limiting amino acids by about 30% for both raw and cooked pork. Cooking had no detrimental effect on amino acid balance. Some examples of small effects of genotype and sex on amino acid composition of pork were shown.

Gross and true ileal digestible amino acid contents of several animal body proteins and their hydrolysates.

Amino acid compositions of ovine muscle, ovine myofibrillar protein, ovine spleen, ovine liver, bovine blood plasma, bovine blood globulins and bovine serum albumin and the amino acid compositions and in vivo (laboratory rat) true ileal amino acid digestibilities of hydrolysates (sequential hydrolysis with Neutrase, Alcalase and Flavourzyme) of these protein sources were determined. True ileal amino acid digestibility differed (P<0.05) among the seven protein hydrolysates. The ovine myofibrillar protein and liver hydrolysates were the most digestible, with a mean true ileal digestibility across all amino acids of 99%. The least digestible protein hydrolysate was bovine serum albumin with a comparable mean true ileal digestibility of 93%. When the digestible amino acid contents were expressed as proportions relative to lysine, considerable differences, across the diverse protein sources, were found in the pattern of predicted absorbed amino acids.

Is pre-operative imaging essential prior to ureteric stone surgery?

INTRODUCTION: The aim of this study was to identify patients not requiring ureteric stone surgery based on pre-operative imaging (within 24 hours) prior to embarking on semirigid ureteroscopy (R-URS) for urolithiasis. METHODS: The imaging of all consecutive patients on whom R-URS for urolithiasis was performed over a 12-month period was reviewed. All patients had undergone a plain x-ray of the kidney, ureters and bladder (KUB), abdominal non-contrast computed tomography (NCCT-KUB) or both on the day of surgery. RESULTS: A total of 96 patients were identified for the study. Stone sizes ranged from 3 mm to 20 mm. Thirteen patients (14%) were cancelled as no stone(s) were identified on pre-operative imaging. Of the patients cancelled, 8 (62%) required NCCT-KUB to confirm spontaneous stone passage. CONCLUSIONS: One in seven patients were stone free on the day of surgery. This negates the need for unnecessary anaesthetic and instrumentation of the urinary tract, with the associated morbidity. Up-to-date imaging prior to embarking on elective ureteric stone surgery is highly recommended.

Antimicrobial effect and mode of action of terpeneless cold-pressed Valencia orange essential oil on methicillin-resistant Staphylococcus aureus.

AIMS: The objectives of this study were to evaluate the antistaphylococcal effect and elucidate the mechanism of action of orange essential oil against antibiotic-resistant Staphylococcus aureus strains. METHODS AND RESULTS: The inhibitory effect of commercial orange essential oil (EO) against six Staph. aureus strains was tested using disc diffusion and agar dilution methods. The mechanism of EO action on MRSA was analysed by transcriptional profiling. Morphological changes of EO-treated Staph. aureus were examined using transmission electron microscopy. Results showed that 0·1% of terpeneless cold-pressed Valencia orange oil (CPV) induced the cell wall stress stimulon consistent with the inhibition of cell wall synthesis. Transmission electron microscopic observation revealed cell lysis and suggested a cell wall lysis-related mechanism of CPV. CONCLUSIONS: CPV inhibits the growth of Staph. aureus, causes gene expression changes consistent with the inhibition of cell wall synthesis, and triggers cell lysis. SIGNIFICANCE AND IMPACT OF THE STUDY: Multiple antibiotics resistance is becoming a serious problem in the management of Staph. aureus infections. In this study, the altered expression of cell wall-associated genes and subsequent cell lysis in MRSA caused by CPV suggest that it may be a potential antimicrobial agent to control antibiotic-resistant Staph. aureus.

The early radiological results of the uncemented Oxford medial compartment knee replacement.

We carried out a prospective investigation into the radiological outcomes of uncemented Oxford medial compartment unicondylar replacement in 220 consecutive patients (231 knees) performed in a single centre with a minimum two-year follow-up. The functional outcomes using the mean Oxford knee score and the mean high-activity arthroplasty score were significantly improved over the pre-operative scores (p < 0.001). There were 196 patients with a two-year radiological examination performed under fluoroscopic guidance, aiming to provide images acceptable for analysis of the bone-implant interface. Of the six tibial zones examined on each knee on the anteroposterior radiograph, only three had a partial radiolucent line. All were in the medial aspect of the tibial base plate (zone 1) and all measured < 1 mm. All of these patients were asymptomatic. There were no radiolucent lines seen around the femoral component or on the lateral view. There was one revision for loosening at one year due to initial inadequate seating of the tibial component. These results confirm that the early uncemented Oxford medial unicompartmental compartmental knee replacements were reliable and the incidence of radiolucent lines was significantly decreased compared with the reported results of cemented versions of this implant. These independent results confirm those of the designing centre.

Improved pain, physical functioning and health status in patients with rheumatoid arthritis treated with CP-690,550, an orally active Janus kinase (JAK) inhibitor: results from a randomised, double-blind, placebo-controlled trial.

OBJECTIVES: To determine the efficacy of CP-690,550 in improving pain, function and health status in patients with moderate to severe active rheumatoid arthritis (RA) and an inadequate response to methotrexate or a tumour necrosis factor alpha inhibitor. METHODS: Patients were randomised equally to placebo, CP-690,550 5, 15 or 30 mg twice daily for 6 weeks, with 6 weeks' follow-up. The patient's assessment of arthritis pain (pain), patient's assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) and Short Form-36 (SF-36) were recorded. RESULTS: At week 6, significantly more patients in the CP-690,550 5, 15 and 30 mg twice-daily groups experienced a 50% improvement in pain compared with placebo (44%, 66%, 78% and 14%, respectively), clinically meaningful reductions in HAQ-DI (> or =0.3 units) (57%, 75%, 76% and 36%, respectively) and clinically meaningful improvements in SF-36 domains and physical and mental components. CONCLUSIONS: CP-690,550 was efficacious in improving the pain, function and health status of patients with RA, from week 1 to week 6.

Chemical composition characteristics of the longissimus and semimembranosus muscles for pigs from New Zealand and Singapore.

A range of composition characteristics of the longissimus (LL) and semimembranosus (SM) muscles were compared between pigs raised in intensive and extensive production systems in New Zealand (NZ), and pigs raised in an intensive system in Indonesia for supply to the Singapore market (n=8/group). Ultimate pH was slightly higher for the Singaporean LL muscles (P<0.05), while LL muscle of the NZ extensive group was redder (higher a(∗) values) and contained more fat (P<0.05). Muscle iron levels were highest for the NZ extensive group and lowest for a lighter group within the Singapore pigs (P<0.05). Differences in fatty acid concentrations, which were also measured in a sample of the belly cut, could largely be attributed to the effects of diet, with higher levels of alpha linolenic acid for the NZ extensive group (P<0.05) due to linseed in the diet, and much higher levels of linoleic acid and the P:S ratio for the Singapore group (P<0.05). Some statistically significant differences in amino acid concentrations were shown between muscles and groups, but they were not large. With respect to compounds with potential bioactive properties, coenzyme Q10, and taurine levels were higher in pork from NZ pigs, and carnosine levels were highest for the NZ intensive group (P<0.05). The LL muscle contained more coenzyme Q10 and taurine, but less carnosine than the SM muscle (P<0.001). It is concluded that some of these composition differences in the pork from the muscles and groups compared may be of commercial importance, but several are likely to have been due to dietary or weight differences.

The influence of diets supplemented with conjugated linoleic acid, selenium, and vitamin E, with or without animal protein, on the quality of pork from female pigs.

Pork from the LM and semimembranosus muscle (SM) of 59 female Duroc-cross pigs with a mean carcass weight of 80.1 kg (SD = 3.2) were assessed for quality. The pigs were grown on diets containing either animal and plant products (the animal group) or plant products only (the plant group), with or without a supplement (0.31% of the diet) containing extra CLA, selenium, and vitamin E. The 45-min postmortem pH of LM was unaffected by dietary treatment (mean 6.44, SD = 0.21), but the ultimate pH (pHu) was lower for the supplemented animal group for both muscles within the animal group (P < 0.04). Water-holding capacity in terms of drip loss for SM and expressed juice levels for LM, but not cooking loss, was also lower for the supplemented animal group (P < 0.01), but this difference was reduced after adjustment to a constant pHu (P < 0.07). Warner-Bratzler shear force (WBSF) values were greater for the plant group for LM only (P < 0.05), both before and after pHu adjustment. Differences between dietary treatment groups for color (L*, a*, and b*) were small and seldom significant before or after pHu adjustment. Sensory assessment of LM samples (with 5% subcutaneous fat added) from 32 pigs (8 per group) for 8 odor notes and 11 flavor notes by a trained analytical sensory panel of 13 people revealed no differences between the groups, except that the percentage of instances in which a rancid odor was detected was greater for the supplemented plant group compared with the control plant group (25 vs. 12%). Differences (P < 0.001) were shown between the muscles such that, relative to SM, LM had lower pHu values, greater drip losses, greater WBSF values, greater L* values, and lower chroma values, but similar levels of cooking loss. It is concluded that the dietary treatments imposed to improve the nutritional value of pork had some effects on certain meat quality parameters, but that the overall effects on appearance and palatability were small and unlikely to be of practical importance.

The influence of diets supplemented with conjugated linoleic acid, selenium, and vitamin E, with or without animal protein, on the composition of pork from female pigs.

The objective of this study was to evaluate the effect of dietary manipulations on the fatty acid composition, Se content, and vitamin E content of pork. Sixty Duroc-cross gilts were randomly allocated at weaning to 1 of 4 dietary treatment groups (n = 15 per group). The 4 experimental diets were based on animal plus plant components or plant components only, with or without the inclusion of a dietary supplement (0.614%) containing CLA, Se, and vitamin E. The growth performance to approximately 100 kg of BW was similar with diets containing animal plus plant components or only plant components. Growth was also similar when either of these diets included the supplement. Inclusion of the supplement led to expected increases in Se and vitamin E contents (P < 0.001) of the LM. The differences found in the fatty acid profile of the lipid in LM, loin subcutaneous fat, and the belly cut (pork belly) between the groups with and without animal components in their diets largely reflected differences in the diet composition. Inclusion of the supplement led to greater CLA contents in all 3 tissues (P < 0.001), and also to lower contents of oleic acid (P < 0.001) and greater contents of stearic acid (P < 0.05), possibly due to an inhibition of stearoyl-CoA desaturase enzyme. The supplement also led to an increase in LM intramuscular fat (P < 0.05), but did not affect P2 fat depths (65 mm lateral to the midline of the spine at the last rib; mean depth of 11.8 mm). It is concluded that changing from a part animal component diet to an all plant diet will not change the growth performance of pigs but changes in the fatty acid profile of pork are likely to occur. It is further concluded that the nutritional value of pork may be successfully enhanced by simultaneously supplementing the diet with CLA, selenium, and vitamin E.

Genetic changes that correlate with the pine-oil disinfectant-reduced susceptibility mechanism of Staphylococcus aureus.

AIMS: To identify factors associated with the Staphylococcus aureus pine-oil disinfectant-reduced-susceptibility (PD(RS)) mechanism and to describe one possible PD(RS) model. METHODS AND RESULTS: Comparative genomic sequencing (CGS) and microarray analysis were utilized to detect mutations and transcriptome alterations that occur in a S. aureus PD(RS) mutant. Mutant analysis, antimicrobial gradient plates, growth studies and 3-hydroxy-3-methylglutaryl coenzyme A synthase assays were then performed to confirm the biological consequences of the 'omics' alterations detected in a PD(RS) mutant. CGS uncovered three mutations in a PD(RS) mutant in a(n): alcohol dehydrogenase (adh), catabolite control protein A (ccpA) and an NADPH-flavin oxidoreductase (frp). These mutations lead to increased growth rates; increased transcription of an NAD-dependent D-lactate dehydrogenase gene (ddh); and increased flux through the mevalonate pathway. PD(RS) mutants demonstrated reduced susceptibility to bacitracin and farnesol, and one PD(RS) mutant displayed upregulation of bacA, a bacitracin-resistance gene. Collectively, this evidence demonstrates altered undecaprenol metabolism in PD(RS) mutants. CONCLUSIONS: The PD(RS) mechanism proposed results from increased catabolic capabilities and increased flux through the mevalonate pathway as well as altered bactoprenol physiology. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel mechanism that bacteria utilize to overcome the killing effects of PD formulations is proposed that is unique from the PD(RS) mechanism of the enterobacteraciae.

Preliminary investigation of the effects of low-level dietary inclusion of fragrant essential oils and oleoresins on pig performance and pork quality.

Since the tissue characteristics of monogastric species are readily influenced by the composition of the feeds they consume, the objectives of this preliminary study were to assess the performance of finisher pigs on diets containing 0.05% of essential oils or oleoresins of rosemary, garlic, oregano, or ginger, and to determine the effect of these diets on pork quality. The pigs preferred the garlic-treated diet, and feed intake and average daily gain were significantly increased although no difference in feed efficiency was observed. Carcass and meat quality attributes were unchanged by dietary treatment, although a tendency towards reduction of lipid oxidation was noted in oregano-fed pork. Sensory panelists were unable to detect a flavour/aroma difference between treated and control pork. These results indicate that a higher level of dietary supplementation may be required in order to effect observable differences in pork characteristics.

Autolytic properties of glycopeptide-intermediate Staphylococcus aureus Mu50.

Whole-cell autolytic activity of prototypical glycopeptide-intermediate Staphylococcus aureus (GISA) Mu50 was reduced versus that of hetero-GISA Mu3 and glycopeptide-susceptible S. aureus, consistent with other GISA strains. In contrast, autolytic activity was relatively high in Mu50 crude cell walls and autolysin extracts against purified cell walls, reflecting the complexities of autolytic activity regulation.

The effect of modified atmosphere packaging with carbon monoxide on the storage quality of master-packaged fresh pork.

Modified atmosphere packaging with carbon dioxide is effective for prolonging shelf-life of fresh meat. Addition of carbon monoxide to the system provides the advantage of enhancing meat colour. The study objective was to determine the effect of CO(2)-MAP+0.4% CO, vs. 100% CO(2)-MAP, on the bacteriology and colour of retail-ready fresh pork stored for 8 weeks in a master-package system. Total plate counts were not affected and listeria was present on meat from both treatments. Colour was enhanced with the inclusion of CO, while no effect on lipid oxidation was observed. Use of CO in MAP provides sufficient storage life and product colour quality to permit shipment of fresh pork to distant markets. However, given the stable fresh colour of CO-treated meat and the lack of inhibition of pathogen growth by CO, there is concern that CO-MAP under certain conditions may pose a food safety risk.

Changes in the forms of iron and in concentrations of taurine, carnosine, coenzyme Q(10), and creatine in beef longissimus muscle with cooking and simulated stomach and duodenal digestion.

Longissimus muscle samples from 31 Angus-cross heifers finished on either a high-concentrate feedlot diet or pasture were used to evaluate the effects of cooking (71°C) on the concentration and forms of iron in the meat, and also on concentrations of the bioactive compounds taurine, carnosine, coenzyme Q(10), creatine and creatinine. For a sub-sample of 15 the effects of pepsin and pancreatin digestion were assessed. For iron, cooking resulted in some overall loss together with a major change from soluble haem and non-haem iron to the insoluble forms, but solubility was regained to a significant extent following digestion. Total haem iron percentage, however, decreased at each step from an initial 88% to a final 61% of total iron. For the bioactive compounds, cooking led to a reduction in taurine, carnosine, coenzyme Q(10), and creatine. The effects of digestion on the bioactive compounds varied. No clear differences were shown in the way in which beef from pasture-finished and feedlot-finished cattle responded to cooking and digestion.

Modelling the electrical properties of bladder tissue--quantifying impedance changes due to inflammation and oedema.

Electrical impedance spectroscopy has been developed as a potential method for the diagnosis of carcinoma in epithelial tissues. An understanding of the influence of structural changes in the tissue on the properties measured using this technique is essential for interpreting measured data and optimization of probe design. In contrast to other tissue types, carcinoma in situ of the bladder gives rise to an increase in electrical impedance over the kHz-MHz frequency range in comparison to normal tissue. Finite element models of the urothelium and the underlying superficial lamina propria have been constructed and solved in order to ascertain the influence of structural changes associated with malignancy, oedema and inflammation on the measured electrical properties of the tissue. Sensitivity analysis of results from a composite tissue model suggests that the increase in lymphocyte density in the lamina propria associated with an inflammatory response to the infiltration of urine into the tissue may explain these unusual electrical properties.

Characterization of Staphylococcus aureus mutants expressing reduced susceptibility to common house-cleaners.

AIMS: To characterize mutants of Staphylococcus aureus expressing reduced susceptibility to house cleaners (HC), assess the impact of the alternative sigma factor SigB on HC susceptibility, and determine the MIC of clinical methicillin-resistant S. aureus (MRSA) to a HC. METHODS AND RESULTS: Susceptibility to HC, HC components, H2O2, vancomycin and oxacillin and physiological parameters were determined for HC-reduced susceptibility (HCRS) mutants, parent strain COL and COLsigB::kan. HCRS mutants selected with three HC expressed reduced susceptibility to multiple HC, HC components, H2O2 and vancomycin. Two unique HCRS mutants also lost the methicillin resistance determinant. In addition, all HCRS mutants exhibited better growth at two temperatures, and one HCRS mutant expressed reduced carotenoid production. COLsigB::kan demonstrated increased susceptibility to all HC and many HC components. sigB operon mutations were not detected in one HCRS mutant background. Of 76 clinical MRSA, 20 exhibited reduced susceptibility to a HC. CONCLUSIONS: HCRS mutants demonstrate altered susceptibility to multiple antimicrobials. While sigB is required for full HC resistance, one HCRS mechanism does not involve sigB operon mutations. Clinical MRSA expressing reduced susceptibility to a common HC were detected. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that HCRS mutants are not protected against, nor selected by, practical HC concentrations.

The escalating challenge of vancomycin resistance in Staphylococcus aureus.

The glycopeptide antibiotic vancomycin is considered indispensable for the treatment of multidrug-resistant Staphylococcus aureus infections, and so the acquisition by these organisms of transmissible glycopeptide resistance elements from enterococci had been anticipated with apprehension. It was therefore a considerable surprise when vancomycin-intermediate S. aureus (VISA) clinical isolates were reported in 1997, with a novel, borderline-resistance phenotype acquired without genetic exchange. Clinical vancomycin-resistant S. aureus (VRSA) were not reported until 2002, expressing high level, transmissible resistance by virtue of vanA resistance determinants within enterococcal transposable elements residing on staphylococcal plasmids. This review will provide an update on the frustratingly variable characteristics of the VISA phenotype, focus on the progress made in understanding the molecular basis of the VISA resistance mechanism from the viewpoint of genetic regulation and cell wall stress response, and summarize the information currently available on VRSA. Finally, alternatives to vancomycin that are already available or nearing approval will be briefly reviewed, with attention to their limitations and potential for resistance development.