Is increased joint loading detrimental to obese patients with knee osteoarthritis? A secondary data analysis from a randomized trial

SummaryObjectiveTo investigate whether increased knee joint loading due to improved ambulatory function and walking speed following weight loss achieved over 16 weeks accelerates symptomatic and structural disease progression over a subsequent 1 year weight maintenance period in an obese population with knee osteoarthritis (OA).MethodsData from a prospective study of weight loss in obese patients with knee OA (the CARtilage in obese knee OsteoarThritis (CAROT) study) were used to determine changes in knee joint compressive loadings (model estimated) during walking after a successful 16 week weight loss intervention. The participants were divided into ‘Unloaders’ (participants that reduced joint loads) and ‘Loaders’ (participants that increased joint loads). The primary symptomatic outcome was changes in knee symptoms, measured with the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire, during a subsequent 52 weeks weight maintenance period. The primary structural outcome was changes in tibiofemoral cartilage loss assessed semi-quantitatively (Boston Leeds Knee Osteoarthritis Score (BLOKS) from MRI after the 52 weight maintenance period.Results157 participants (82% of the CAROT cohort) with medial and/or lateral knee OA were classified as Unloaders (n = 100) or Loaders (n = 57). The groups showed similar significant changes in symptoms (group difference: −2.4 KOOS points [95% CI −6.8:1.9]) and cartilage loss (group difference: −0.06 BLOKS points [95% CI −0.22:0.11) after 1 year, with no statistically significant differences between Loaders and Unloaders.ConclusionFor obese patients undergoing a significant weight loss, increased knee joint loading for 1 year was not associated with accelerated symptomatic and structural disease progression compared to a similar weight loss group that had reduced ambulatory compressive knee joint loads.Clinicaltrials.govNCT00655941

The 2017 reversal of the Beaufort Gyre: Can dynamic thickening of a seasonal ice cover during a reversal limit summer ice melt in the Beaufort Sea?

During winter 2017 the semi‐permanent Beaufort High collapsed and the anticyclonic Beaufort Gyre reversed. The reversal drove eastward ice motion through the Western Arctic, causing sea ice to converge against Banks Island, and halted the circulation of multiyear sea ice via the gyre, preventing its replenishment in the Beaufort Sea. Prior to the reversal, an anomalously thin seasonal ice cover had formed in the Beaufort following ice‐free conditions during September 2016. With the onset of the reversal in January 2017, convergence drove uncharacteristic dynamic thickening during winter. By the end of March, despite seasonal ice comprising 97% of the ice cover, the reversal created the thickest, roughest and most voluminous regional ice cover of the CryoSat‐2 record. Within the Beaufort Sea, previous work has shown that winter ice export can precondition the region for increased summer ice melt, but that a short reversal during April 2013 contributed to a reduction in summer ice loss. Hence the deformed ice cover at the end of winter 2017 could be expected to limit summer melt. In spite of this, the Beaufort ice cover fell to its fourth lowest September area as the gyre re‐established during April and divergent ice drift broke up the pack, negating the reversal's earlier preconditioning. Our work highlights that dynamic winter thickening of a regional sea ice cover, for instance during a gyre reversal, offers the potential to limit summer ice loss, but that dynamic forcing during spring dictates whether this conditioning carries through to the melt season

Stage-associated overexpression of the ubiquitin-like protein, ISG15, in bladder cancer

Bladder cancer is among the most prevalent malignancies, and is characterised by frequent tumour recurrences and localised inflammation, which may promote tissue invasion and metastasis. Microarray analysis was used to compare gene expression in normal bladder urothelium with that in tumours at different stages of progression. The innate immune response gene, interferon-stimulated gene 15 kDa (ISG15, GIP2), was highly expressed at all stages of bladder cancer as compared to normal urothelium. Western blotting revealed a tumour-associated expression of ISG15 protein. ISG15 exhibited a stage-associated expression, with significantly (P<0.05) higher levels of ISG15 protein in muscle-invasive T2–T4 tumours, compared with normal urothelium. Although ISG15 is involved in the primary immune response, ISG15 expression did not correlate with bladder inflammation. However, immunohistochemical staining revealed expression of ISG15 protein in both cancer cells and stromal immune cells. Interestingly, a significant fraction of ISG15 protein was localised to the nuclei of tumour cells, whereas no nuclear ISG15 staining was observed in ISG15-positive stromal cells. Taken together, our findings identify ISG15 as a novel component of bladder cancer-associated gene expression

Dysregulation of the transcription factors SOX4, CBFB and SMARCC1 correlates with outcome of colorectal cancer

The aim of this study was to identify deregulated transcription factors (TFs) in colorectal cancer (CRC) and to evaluate their relation with the recurrence of stage II CRC and overall survival. Microarray-based transcript profiles of 20 normal mucosas and 424 CRC samples were used to identify 51 TFs displaying differential transcript levels between normal mucosa and CRC. For a subset of these we provide in vitro evidence that deregulation of the Wnt signalling pathway can lead to the alterations observed in tissues. Furthermore, in two independent cohorts of microsatellite-stable stage II cancers we found that high SOX4 transcript levels correlated with recurrence (HR 2.7; 95% CI, 1.2–6.0; P=0.01). Analyses of ∼1000 stage I–III adenocarcinomas, by immunohistochemistry, revealed that patients with tumours displaying high levels of CBFB and SMARCC1 proteins had a significantly better overall survival rate (P=0.0001 and P=0.0275, respectively) than patients with low levels. Multivariate analyses revealed that a high CBFB protein level was an independent predictor of survival. In conclusion, several of the identified TFs seem to be involved in the progression of CRC

Gene expression profiling of noninvasive primary urothelial tumours using microarrays

At present, the mechanism leading to bladder cancer is still poorly understood, and our knowledge about early events in tumorigenesis is limited. This study describes the changes in gene expression occurring during the neoplastic transition from normal bladder urothelium to primary Ta tumours. Using DNA microarrays, we identified novel differentially expressed genes in Ta tumours compared to normal bladder, and genes that were altered in high-grade tumours. Among the mostly changed genes between normal bladder and Ta tumours, we found genes related to the cytoskeleton (keratin 7 and syndecan 1), and transcription (high mobility group AT-hook 1). Altered genes in high-grade tumours were related to cell cycle (cyclin-dependent kinase 4) and transcription (jun d proto-oncogene). Furthermore, we showed the presence of high keratin 7 transcript expression in bladder cancer, and Western blotting analysis revealed three major molecular isoforms of keratin 7 in the tissues. These could be detected in urine sediments from bladder tumour patients