Assessing the consultation: methods of observing trainees in general practice.

We compared two different methods of observing trainees at work in general practice: the traditional one of a senior or training general practitioner sitting in during selected surgeries and the more modern video recording, with the patients'' written consent. Patients who had experienced the presence of a second doctor during the consultation were less likely to show an increase in arousal after their consultations than those who had been recorded on video. Patients who refused consent to be recorded were more highly stressed than those who agreed and showed smaller decreases in stress after consultations. The presence of two doctors generated fewer reductions in stress after the consultation than video recording did, but this was a non-significant trend. The group that was recorded on video did not differ appreciably from a control group in changes in stress or arousal.     

Genome-Wide Relatedness of Treponema pedis,from Gingiva and Necrotic Skin Lesions of Pigs,with the Human Oral Pathogen Treponema denticola

Treponema pedis and T. denticola are two genetically related species with different origins of isolation. Treponema denticola is part of the human oral microbiota and is associated with periodontitis while T. pedis has been isolated from skin lesions in animals, e.g., digital dermatitis in cattle and necrotic ulcers in pigs. Although multiple Treponema phylotypes may exist in ulcerative lesions in pigs, T. pedis appears to be a predominant spirochete in these lesions. Treponema pedis can also be present in pig gingiva. In this study, we determined the complete genome sequence of T. pedis strain T A4, isolated from a porcine necrotic ear lesion, and compared its genome with that of T. denticola. Most genes in T. pedis were homologous to those in T. denticola and the two species were similar in general genomic features such as size, G+C content, and number of genes. In addition, many homologues of specific virulence-related genes in T. denticola were found in T. pedis. Comparing a selected pair of strains will usually not give a complete picture of the relatedness between two species. We therefore complemented the analysis with draft genomes from six T. pedis isolates, originating from gingiva and necrotic ulcers in pigs, and from twelve T. denticola strains. Each strain carried a considerable amount of accessory genetic material, of which a large part was strain specific. There was also extensive sequence variability in putative virulence-related genes between strains belonging to the same species. Signs of lateral gene-transfer events from bacteria known to colonize oral environments were found. This suggests that the oral cavity is an important habitat for T. pedis. In summary, we found extensive genomic similarities between T. pedis and T. denticola but also large variability within each species.     

The effect of deprivation on variations in general practitioners' referral rates: a cross sectional study of computerised data on new medical and surgical outpatient referrals in Nottinghamshire.

OBJECTIVE: To determine the effect of deprivation on variations in general practitioners'' referral rates using the Jarman underprivileged area (UPA(8)) score as a proxy measure. DESIGN: Cross sectional survey of new medical and surgical referrals from general practices to hospitals (determined from hospital activity data). SETTING: All of the 183 general practices in Nottinghamshire and all of the 19 hospitals in Trent region. MAIN OUTCOME MEASURES: The relation between the referral rates per 1000 registered patients and the practice population''s UPA(8) score (calculated on the basis of electoral ward), with adjustment for the number of partners, percentage of patients aged over 65 years, and fundholding status of each practice. RESULTS: There was a significant independent association between deprivation, as measured by the UPA(8) score, and high total referral rates and high medical referral rates (P < 0.0001). The UPA(8) score alone explained 23% of the total variation in total referral rates and 32% of the variation in medical referral rates. On multivariate analysis, where partnership size, fundholding status, and percentage of men and women aged over 65 years were included, the UPA(8) score explained 29% and 35% of the variation in total and medical referral rates respectively. CONCLUSION: Of the variables studied, the UPA(8) score was the strongest predictor of variations in referral rates. This association is most likely to be through a link with morbidity, although it could reflect differences in patients'' perceptions, doctors'' behaviour, or the use and provision of services.     

Arylsulfatase K,a Novel Lysosomal Sulfatase

The human sulfatase family has 17 members, 13 of which have been characterized biochemically. These enzymes specifically hydrolyze sulfate esters in glycosaminoglycans, sulfolipids, or steroid sulfates, thereby playing key roles in cellular degradation, cell signaling, and hormone regulation. The loss of sulfatase activity has been linked to severe pathophysiological conditions such as lysosomal storage disorders, developmental abnormalities, or cancer. A novel member of this family, arylsulfatase K (ARSK), was identified bioinformatically through its conserved sulfatase signature sequence directing posttranslational generation of the catalytic formylglycine residue in sulfatases. However, overall sequence identity of ARSK with other human sulfatases is low (18–22%). Here we demonstrate that ARSK indeed shows desulfation activity toward arylsulfate pseudosubstrates. When expressed in human cells, ARSK was detected as a 68-kDa glycoprotein carrying at least four N-glycans of both the complex and high-mannose type. Purified ARSK turned over p-nitrocatechol and p-nitrophenyl sulfate. This activity was dependent on cysteine 80, which was verified to undergo conversion to formylglycine. Kinetic parameters were similar to those of several lysosomal sulfatases involved in degradation of sulfated glycosaminoglycans. An acidic pH optimum (∼4.6) and colocalization with LAMP1 verified lysosomal functioning of ARSK. Further, it carries mannose 6-phosphate, indicating lysosomal sorting via mannose 6-phosphate receptors. ARSK mRNA expression was found in all tissues tested, suggesting a ubiquitous physiological substrate and a so far non-classified lysosomal storage disorder in the case of ARSK deficiency, as shown before for all other lysosomal sulfatases.