BACKGROUND: The level of circulating interleukin 10 (IL‐10) is elevated in a proportion of patients with hepatocellular carcinoma (HCC). The objective of the current study was to evaluate the prognostic significance of serum the IL‐10 level in patients with unresectable HCC. METHODS: Patients with unresectable HCC who provided serum at the time of diagnosis were enrolled prospectively in the study. The level of circulating IL‐10 in serum samples was determined by enzyme‐linked immunosorbent assay. The association of the IL‐10 level with overall survival was evaluated in relation to sociodemographics, liver function, hepatitis B viral load, and tumor staging. RESULTS: In total, 222 patients were recruited; of these, 82.4% were positive for hepatitis B virus surface antigen, and 65.8% had Barcelona Clinic Liver Cancer stage C disease. The mean log IL‐10 level was 1.1 pg/mL, and 146 patients had an IL‐10 level >1 pg/mL (high IL‐10 group). The high IL‐10 group had worse overall survival than the low IL‐10 group (5.0 months vs 14.9 months; hazard ratio, 2.192; P < .0001). The IL‐10 level was associated with worse hepatic function and with a high alanine transaminase (ALT) level. The IL‐10 level remained an independent prognostic factor (hazard ratio, 1.824; P = .0005) after adjustment for sociodemographics, tumor staging, treatment, Child‐Pugh stage, and ALT level. The IL‐10 level also subdivided patients into 2 populations with distinct survival (10.2 months vs 3.5 months; P = .0027). CONCLUSIONS: The serum IL‐10 level was identified as an independent prognostic factor for unresectable HCC. The current findings suggested that an elevated IL‐10 level may be related to hepatic injury caused by cirrhotic processes rather than tumor load. The authors concluded that the IL‐10 level offers additional prognostic value to the existing tumor staging systems. Cancer 2012. © 2011 American Cancer Society.

There appears a linear relationship between small increases in running speed and cardiovascular health benefits. Encouraging or coaching recreational runners to increase their running speed to derive these health benefits might be more effective if their joint level kinematic and kinetic strategy was understood. The aim of this investigation was to compare the peak sagittal plane motions, moments, and powers of the hip, knee and ankle at 85%, 100%, 115% and 130% of self-selected running speed. Overground running data were collected in 12 recreational runners (6 women, 6 men) with a full body marker set using a 12-camera Vicon MX system with an AMTI force plate. Kinematics and kinetics were analyzed with Vicon Nexus software. Participants chose to run at 2.6 ± 0.5 m/s (85%); 3.0 ± 0.5 m/s (100%); 3.3 ± 0.5 m/s (115%); and 3.7 ± 0.5 m/s (130%); these four speeds approximately correspond to 6:24-, 5:33-, 5:03-, and 4:30-min kilometer running paces. Running speed had a significant effect (P < 0.05) on peak kinematic and kinetic variables of the hips, knees and ankles, with peak sagittal hip moments invariant (P > 0.54) and the peak sagittal ankle power generation (P < 0.0001) the most highly responsive variable. The timing of the peak sagittal extensor moments and powers at the hip, knee and ankle were distributed across stance in a sequential manner. This study shows that running speed affects lower limb joint kinematics and kinetics and suggests that specific intersegmental kinetic strategies might exist across the narrow range of running speeds.

We hypothesized that axitinib is active with an improved safety profile in nasopharyngeal carcinoma (NPC). We evaluated axitinib in preclinical models of NPC and studied its efficacy in a phase II clinical trial in recurrent or metastatic NPC patients who progressed after at least one line of prior platinum-based chemotherapy. We excluded patients with local recurrence or vascular invasion. Axitinib was started at 5 mg twice daily in continuous 4-week cycles. Primary endpoint was clinical benefit rate (CBR), defined as the percentage of patients achieving complete response, partial response, or stable disease by RECIST criteria for more than 3 months. We recruited 40 patients, who received a median of 3 lines of prior chemotherapy. Axitinib was administered for a mean of 5.6 cycles, with 16 patients (40%) receiving ≥6 cycles. Of 37 patients evaluable for response, CBR was 78.4% (95% CI, 65.6%-91.2%) at 3 months and 43.2% (30.4%-56.1%) at 6 months. Grade 3/4 toxicities were uncommon, including hypertension (8%), diarrhea (5%), weight loss (5%), and pain (5%). All hemorrhagic events were grade 1 (15%) or grade 2 (3%). Elevated diastolic blood pressure during the first 3 months of axitinib treatment was significantly associated with improved overall survival (HR, 0.29; 95% CI, 0.13-0.64, = 0.0012). Patient-reported fatigue symptom was associated with hypothyroidism ( = 0.039). Axitinib PK parameters (C and AUC) were significantly correlated with tumor response, toxicity, and serum thyroid-stimulating hormone changes. Axitinib achieved durable disease control with a favorable safety profile in heavily pretreated NPC patients. .

Among the conventional and exploratory circulating inflammatory markers, higher CRP, lower albumin and higher interleukin-8 were independent prognosticators. By combining these factors, a simple and accurate inflammatory index could be constructed.

Transcription factors (TFs) are often used repeatedly during development and homeostasis to control distinct processes in the same and/or different cellular contexts. Considering the limited number of TFs in the genome and the tremendous number of events that need to be regulated, re-use of TFs is necessary. We analyzed how the expression of the homeobox TF, orthodenticle homeobox 2 (Otx2), is regulated in a cell type- and stage-specific manner during development in the mouse retina. We identified seven Otx2 cis-regulatory modules (CRMs), among which the O5, O7 and O9 CRMs mark three distinct cellular contexts of Otx2 expression. We discovered that Otx2, Crx and Sox2, which are well-known TFs regulating retinal development, bind to and activate the O5, O7 or O9 CRMs, respectively. The chromatin status of these three CRMs was found to be distinct in vivo in different retinal cell types and at different stages. We conclude that retinal cells use a cohort of TFs with different expression patterns and multiple CRMs with different chromatin configurations to regulate the expression of Otx2 precisely.

Aims-To evaluate the usefulness of a single-tube nested polymerase chain reaction (PCR) assay in the diagnosis of tuberculosis in 1497 pulmonary and 536 extrapulmonary specimens. Methods-A single-tube nested PCR, utilising two sets of primers with different melting temperatures (88'C for external primers; 70°C for internal primers) to augment sensitivity and specificity without increasing the risk of amplicon contamination, was evaluated. Specimens were initially tested for the repetitive IS6110 sequences and if negative, retested for the universal 38 kilodalton sequence and for inhibitors. dUTP/Uracil-N-glycosylase and Instagene treatment were used to minimise contamination and the effect of inhibitors, respectively. Results-Using culture as the gold standard, the overall sensitivity of the assay was 89% for pulmonary and 42% for extrapulmonary specimens. Sensitivity varied greatly with respect to sample type (92% for follow up specimens from a chest hospital and 70% for non-follow up specimens from a general hospital). The smear positivity rates were 15% for extrapulmonary specimens, and 69% and 45%, respectively, for follow up and non-follow up specimens from pulmonary sites. Specificity was 99.7%. Inhibitors were present more frequently in extrapulmonary than in pulmonary specimens (13.4% v 2.7%). Conclusion-Despite the high sensitivity ofthe PCR assay for the diagnosis oftuberculosis in pulmonary specimens, it was less effective in the extrapulmonary samples. This is probably because of the lower bacterial load in extrapulmonary specimens, the presence of more inhibitors adversely affecting the PCR assay and the higher volume of specimens used for culture.

Aims-To assess the routine use of a polymerase chain reaction (PCR) assay for the direct detection of Mycobacterium tuberculosis in expectorated sputum specimens. Methods-A pair of primers (20-mer) were designed to amplify the 38 kilodalton protein of M tuberculosis. The specificity of the assay was evaluated in 31 M tuberculosis strains, 15 atypical mycobacterium species, and several commensal bacteria of the upper respiratory tract. The assay was subsequently applied to 519 sputum specimens from 85 inpatients of a chest hospital in Hong Kong.Results-An amplified product of 239 base pairs was found in all M tuberculosis strains, standard strains of M bovis, and M africanum but not in the other bacterial strains tested. For the 51 patients with pulmonary radiographic lesions, the diagnosis of pulmonary tuberculosis was subsequently confirmed by both culture and PCR in 41 of them. Five patients who were treated before admission were positive by PCR alone. All but one patient in the control group (patients with acute exacerbation of chronic obstructive airway diseases) or those with atypical mycobacterial diseases were PCR negative. The PCR remained positive after four weeks of anti-tuberculosis treatment in 29 patients, 16 of whom had become culture negative. Conclusion-This PCR assay is a useful technique for the diagnosis of untreated and recently treated cases of pulmonary tuberculosis.

A large number of surgical techniques have been described to prevent recurrent patellofemoral instability in the pediatric population, including both proximal and distal realignment procedures. The wide variety of treatment options highlights the lack of agreement as to the best surgical approach. However, when a comprehensive exam and workup are paired with a surgical plan to address each of the identified abnormalities, outcomes are predictably good. Patellar instability is a common knee disorder in the skeletally immature patient that presents a unique set of challenges. Rates of re-dislocation in pediatric and adolescent patients are higher than in their adult counterparts. Careful consideration of the physeal and apophyseal anatomy is essential in these patients. While the majority of primary patellar instability events can be treated conservatively, multiple events often require surgical intervention.