Dysregulation of the suppressor of cytokine signalling 3-signal transducer and activator of transcription-3 pathway in the aetiopathogenesis of Sjögren's syndrome.

The suppressor of cytokine signalling 3 (SOCS3) negatively regulates the Janus kinase (JAK)/signal transducer and activator of transcription-3 (STAT-3)/interleukin (IL)-17 pathway. The proinflammatory cytokine IL-17 is over-expressed in Sjögren's syndrome (SS) and is a key factor in its pathogenesis. We hypothesized that IL-17 over-expression in SS results from ineffective regulation by SOCS3. The expression of SOCS3 was analysed in peripheral blood mononuclear cells (PBMC) from SS cases, sicca controls (SC) and healthy controls (HC) and tissue samples from SS, SC and healthy salivary glands (HSG). PBMC and salivary gland tissue from SS and controls were dual-immunostained for SOCS3 and IL-17. IL-6-stimulated PBMC from SS and controls were evaluated for time-dependent STAT-3 activation and SOCS3 induction, and for IL-17 expression. Immunoblotting revealed greater levels of SOCS3 in PBMC from SS than SC (P = 0·017) or HC (P < 0·001). Similarly, the proportion of salivary-gland tissue cells staining for SOCS3 was significantly higher in SS than SC (P = 0·029) or HSG (P = 0·021). The cells in PBMC/salivary gland samples from controls predominantly expressed either SOCS3 or IL-17. However, there was a high frequency of SOCS3/IL-17 co-expression within cells of SS samples. IL-6-stimulation of PBMC from SS cases revealed prolonged activation of STAT-3 with reduced negative regulation by SOCS3, and enhanced expression of IL-17. This study showed that SOCS3 expression is up-regulated in SS. However, the absence in SS of the normal inverse relationship between SOCS3 and pSTAT-3/IL-17 indicates a functional disturbance in this signalling cascade. Consequently, a reduction in function, rather than a reduction in expression of SOCS3 accounts for the unregulated expression of IL-17 in SS, and may play a crucial role in aetiopathogenesis.

Rapid molecular detection of tuberculosis and rifampicin drug resistance: retrospective analysis of a national U.K. molecular service over the last decade.

BACKGROUND: Fast and reliable detection of Mycobacterium tuberculosis complex (MTBC) and drug resistance is crucial in establishing effective treatment and enforcing timely public health measures. METHODS: The authors analysed the performance of a national U.K. molecular diagnostic service over a decade, based on the use of a line probe assay (Innolipa, LiPA) compared with conventional liquid and solid cultures with rapid molecular identification and culture-based drug resistance testing. FINDINGS: Data were available for 7836 consecutive patient samples using LiPA and the reference microbiological technique (conventional liquid and solid cultures with rapid molecular identification and culture-based drug resistance testing). For all sputum specimens (n=3382) the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for MTBC detection were 93.4%, 85.6%, 92.7%, 86.9% and 90.7%; the equivalent values for smear-positive sputum specimens (n=2606) were 94.7%, 80.9%, 93.9%, 83.3% and 91.3%. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for detection of rifampicin resistance in all sputum samples (n=1667) were 92.1%, 99.3%, 89.4%, 99.5% and 98.9%, respectively; the equivalent values for smear-positive sputum specimens (n=1477) were 93.3%, 99.3%, 87.5%, 99.6% and 99%. Between January 2006 and December 2008, LiPA saved 25.3 and 32.2 days for TB diagnosis and rifampicin resistance of smear-positive samples, respectively. INTERPRETATION: A molecular diagnostic service, using a non-automated line probe assay approach, provides a rapid and reliable national service for diagnosing MTBC and rifampicin resistance.

Screening for oral cancer utilising risk-factor analysis is ineffective in high-risk populations.

Screening for oral cancer by direct visual examination is believed to be ineffective because of the difficulty in differentiating a small number of malignancies from the much more prevalent benign oral mucosal lesions (OML) that are found in high-risk individuals. Standardised clinical diagnoses were recorded for all the OMLs identified during oral visual examination of 1111 individuals with risk factors for oral cancer, including tobacco and areca nut (paan) consumption. Suspicious lesions were referred for biopsy and definitive diagnosis. A total of 1438 OMLs with 32 different clinical diagnoses were identified in 604 participants. Analysis of referrals revealed two distinct groups: visually benign lesions (VBLs) none of which was referred, and visually complex lesions (VCLs) comprising 661 OMLs with nine different clinical diagnoses. After biopsy the VCLs included known potentially malignant disorders (PMDs) as well as benign lesions such as paan mucositis. VCLs (but not VBLs) share risk factors with oral cancer (p<0.05 for paan 5.82 (CI: 1.98 to 8.43), and smoking 3.59 (CI: 1.12 to 4.47)). They are clinically indistinguishable from, but much more prevalent than, oral cancer, and most will never undergo malignant change. They therefore can prevent dentists from accurately detecting malignancy during the clinical examination of high-risk patients. However, they can easily be differentiated from other benign lesions by visual examination alone. Further research into diagnostic technology is needed to help differentiate them from oral cancers.

Oral health and related quality of life status in patients from UK and Turkey: a comparative study in Behcet's disease.

BACKGROUND: The aim of this study was to evaluate and compare oral health-related quality of life (oral QoL) in patients from UK and Turkey with Behcet's disease (BD). METHODS: Thirty-one BD patients from UK (F/M: 18/13, mean age: 41.8 +/- 11.5 years) and Turkey (F/M: 18/13, mean age: 41.5 +/- 10.3) who were matched according to age and gender were included in the study. All patients had active oral ulcers. Oral QoL was assessed by Oral Health Impact Profile-14 (OHIP-14). Oral health was evaluated by dental and periodontal indices. RESULTS: No significant difference was found in OHIP-14 scores between patients from UK (22.7 +/- 14.4) and Turkey (20.4 +/- 14.3) (P = 0.709). The OHIP-14 score correlated with the healing time of oral ulcers in UK (r = 0.4, P = 0.04) and the number of oral ulcers in Turkey (r = 0.4, P = 0.012). The number of oral ulcers per month was significantly higher in UK (3.3 +/- 2.8) compared with that in Turkey (1.5 +/- 2.5) (P = 0.014). However, the number of filled teeth and frequency of tooth brushing were significantly lower in patients from Turkey compared with those in UK (P = 0.000). Similarly, the duration since the last dental visit (5.1 +/- 7.2 months) was significantly lower in UK compared with that in Turkey (28.6 +/- 23.7 months) (P = 0.000). CONCLUSIONS: Oral QoL was similar in patients from UK and Turkey with active oral ulcers. However, the number of oral ulcers was observed to be higher in UK. As expected, a lower utilization rate of dental services might have led to a poorer oral health in patients from Turkey.