Lack of robust methods for establishment and expansion of pluripotent human embryonic stem (hES) cells still hampers development of cell therapy. Laminins (LN) are a family of highly cell-type specific basement membrane proteins important for cell adhesion, differentiation, migration and phenotype stability. Here we produce and isolate a human recombinant LN-521 isoform and develop a cell culture matrix containing LN-521 and E-cadherin, which both localize to stem cell niches in vivo. This matrix allows clonal derivation, clonal survival and long-term self-renewal of hES cells under completely chemically defined and xeno-free conditions without ROCK inhibitors. Neither LN-521 nor E-cadherin alone enable clonal survival of hES cells. The LN-521/E-cadherin matrix allows hES cell line derivation from blastocyst inner cell mass and single blastomere cells without a need to destroy the embryo. This method can facilitate the generation of hES cell lines for development of different cell types for regenerative medicine purposes.

A retro-prospective cohort study by Weihong Chen and colleagues provides new estimates for the risk of total and cause-specific mortality due to long-term silica dust exposure among Chinese workers.

Postoperative pain management remains a significant challenge for all healthcare providers. The objective of this systematic review was to quantitatively evaluate the efficacy of acupuncture and related techniques as adjunct analgesics for acute postoperative pain management. We searched the databases of Medline (1966-2007), CINAHL, The Cochrane Central Register of Controlled Trials (2006), and Scopus for randomized controlled trials (RCTs) using acupuncture for postoperative pain management. We extracted data about postoperative opioid consumption, postoperative pain intensity, and opioid-related side-effects. Combined data were analysed using a random effects model. Fifteen RCTs comparing acupuncture with sham control in the management of acute postoperative pain were included. Weighted mean difference for cumulative opioid analgesic consumption was -3.14 mg (95% confidence interval, CI: -5.15, -1.14), -8.33 mg (95% CI: -11.06, -5.61), and -9.14 mg (95% CI: -16.07, -2.22) at 8, 24, and 72 h, respectively. Postoperative pain intensity (visual analogue scale, 0-100 mm) was also significantly decreased in the acupuncture group at 8 and 72 h compared with the control group. The acupuncture treatment group was associated with a lower incidence of opioid-related side-effects such as nausea (relative risk, RR: 0.67; 95% CI: 0.53, 0.86), dizziness (RR: 0.65; 95% CI: 0.52, 0.81), sedation (RR: 0.78; 95% CI: 0.61, 0.99), pruritus (RR: 0.75; 95% CI: 0.59, 0.96), and urinary retention (RR: 0.29; 95% CI: 0.12, 0.74). Perioperative acupuncture may be a useful adjunct for acute postoperative pain management.

Objectives-DiVerent prevalences of generalised osteoarthritis (GOA) in patients with knee and hip OA have been reported. The aim of this investigation was to evaluate radiographic and clinical patterns of disease in a hospital based population of patient subgroups with advanced hip and knee OA and to compare the prevalence of GOA in patients with hip or knee OA, taking potential confounding factors into account. Methods-420 patients with hip OA and 389 patients with knee OA scheduled for unilateral total joint replacement in four hospitals underwent radiographic analysis of ipsilateral and contralateral hip or knee joint and both hands in addition to a standardised interview and clinical examination. According to the severity of radiographic changes in the contralateral joints (using Kellgren-Lawrence > grade 2 as case definition) participants were classified as having either unilateral or bilateral OA. If radiographic changes of two joint groups of the hands (first carpometacarpal joint and proximal/distal interphalangeal joints defined as two separate joint groups) were present, patients were categorised as having GOA. Results-Patients with hip OA were younger (mean age 60.4 years) and less likely to be female (52.4%) than patients with knee OA (66.3 years and 72.5% respectively). Intensity of pain and functional impairment at hospital admission was similar in both groups, while patients with knee OA had a longer symptom duration (median 10 years) compared with patients with hip OA (5 years). In 41.7% of patients with hip OA and 33.4% of patients with knee OA an underlying pathological condition could be observed in the replaced joint, which allowed a classification as secondary OA. Some 82.1% of patients with hip and 87.4% of patients with knee OA had radiographic changes in their contralateral joints (bilateral disease). The prevalence of GOA increased with age and was higher in female patients. GOA was observed more often in patients with knee OA than in patients with hip OA (34.9% versus 19.3%; OR=2.24; 95% CI: 1.56, 3.21). Adjustment for the diVerent age and sex distribution in both patient groups, however, takes away most of the diVerence (OR=1.32; 95% CI: 0.89, 1.96). Conclusion-The crude results confirm previous reports as well as the clinical impression of GOA being more prevalent in patients with advanced knee OA than in patients with advanced hip OA. However, these diVerent patterns might be attributed to a large part to a diVerent distribution of age and sex in these hospital based populations.

Crystalline silica has been classified as a human carcinogen by the International Agency for Research on Cancer (Lyon, France); however, few previous studies have provided quantitative data on silica exposure, silicosis, and/or smoking. We investigated a cohort in China (in 1960–2003) of 34,018 workers without exposure to carcinogenic confounders. Cumulative silica exposure was estimated by linking a job-exposure matrix to work history. Cox proportional hazards model was used to conduct exposure-response analysis and risk assessment. During a mean 34.5-year follow-up, 546 lung cancer deaths were identified. Categorical analyses by quartiles of cumulative silica exposure (using a 25-year lag) yielded hazard ratios of 1.26, 1.54, 1.68, and 1.70, respectively, compared with the unexposed group. Monotonic exposure-response trends were observed among nonsilicotics (P for trend < 0.001). Analyses using splines showed similar trends. The joint effect of silica and smoking was more than additive and close to multiplicative. For workers exposed from ages 20 to 65 years at 0.1 mg/m3 of silica exposure, the estimated excess lifetime risk (through age 75 years) was 0.51%. These findings confirm silica as a human carcinogen and suggest that current exposure limits in many countries might be insufficient to protect workers from lung cancer. They also indicate that smoking cessation could help reduce lung cancer risk for silica-exposed individuals.

ObjectiveOsteoarthritis of the hip (OA) is a common degenerative disorder of the joint cartilage that presents a major public health problem worldwide. While intrinsic risk factors (e.g, body mass and morphology) have been identified, external risk factors are not well understood. In this systematic review, the evidence for workload as a risk factor for hip OA is summarized and used to derive recommendations for prevention and further research.MethodsEpidemiological studies on workload or occupation and osteoarthritis of the hip were identified through database and bibliography searches. Using pre-defined quality criteria, 30 studies were selected for critical evaluation; six of these provided quantitative exposure data.ResultsStudy results were too heterogeneous to develop pooled risk estimates by specific work activities. The weight of evidence favors a graded association between long-term exposure to heavy lifting and risk of hip OA. Long-term exposure to standing at work might also increase the risk of hip OA.ConclusionsIt is not possible to estimate a quantitative dose-response relationship between workload and hip OA using existing data, but there is enough evidence available to identify job-related heavy lifting and standing as hazards, and thus to begin developing recommendations for preventing hip OA by limiting the amount and duration of these activities. Future research to identify specific risk factors for work-related hip OA should focus on implementing rigorous study methods with quantitative exposure measures and objective diagnostic criteria.

Highlights d LN-221 enables production of hESC-derived human cardiovascular progenitors d Bulk and single-cell RNA-seq data reveal highly reproducible differentiation d Cardiovascular progenitors survive in vivo and form human muscle fiber bundles d Improvement in heart function after cell transplantation

A reliable radiographic severity grading of hip and knee OA is possible with the application of global scores and individual features, if joint specific items are selected and readers are trained enough.