A Method for Non-experts in Assessing Exposure to Risk Factors for Work-related Musculoskeletal Disorders—ERIN

A practical method for non-experts in assessing exposure to risk factors for work-related musculoskeletal disorders (WMSDs) is presented. Evaluación del Riesgo Individual (Individual Risk Assessment) (ERIN) is based on available ergonomic tools, epidemiological evidence and the joint IEA-WHO project for developing WMSDs risk management in developing countries. ERIN focuses primarily on the interaction of some physical workplace factors but also includes the workers’ assessment. A scoring system has been proposed to indicate the level of intervention required to reduce the risk of injury. A worksheet has also been designed for increasing the usability of the method. Preliminary tests show that it is easy and quick to use, but further work is needed to establish its reliability and validity. The use of ERIN can contribute to the prevention of WMSDs in Cuba and other developing countries.     

Anti-Bv8 Antibody and Metronomic Gemcitabine Improve Pancreatic Adenocarcinoma Treatment Outcome Following Weekly Gemcitabine Therapy

Weekly gemcitabine therapy is the major treatment offered for patients with pancreatic adenocarcinoma cancer; however, relative resistance of tumor cells to chemotherapy, rapid regrowth, and metastasis are the main causes of death within a year. Recently, the daily continuous administration of chemotherapy in low doses – called metronomic chemotherapy (MC) – has been shown to inhibit primary tumor growth and delay metastases in several tumor types; however, its use as a single therapy is still in question due to its moderate therapeutic benefit. Here, we show that the combination of weekly gemcitabine with MC of the same drug delays tumor regrowth and inhibits metastasis in mice implanted orthotopically with pancreatic tumors. We further demonstrate that weekly gemcitabine, but not continuous MC gemcitabine or the combination of the two drug regimens, promotes rebound myeloid-derived suppressor cell (MDSC) mobilization and increases angiogenesis in this tumor model. Furthermore, Bv8 is highly expressed in MDSCs colonizing pancreatic tumors in mice treated with weekly gemcitabine compared to MC gemcitabine or the combination of the two regimens. Blocking Bv8 with antibodies in weekly gemcitabine-treated mice results in a significant reduction in tumor regrowth, angiogenesis, and metastasis. Overall, our results suggest that pro-tumorigenic effects induced by weekly gemcitabine are mediated in part by MDSCs expressing Bv8. Therefore, both Bv8 inhibition and MC can be used as legitimate ''add-on'' treatments for preventing post-chemotherapy pancreatic cancer recurrence, progression, and metastasis following weekly gemcitabine therapy.     

Tumor‐derived microparticles induce bone marrow‐derived cell mobilization and tumor homing: A process regulated by osteopontin

Acute chemotherapy can induce rapid bone‐marrow derived pro‐angiogenic cell (BMDC) mobilization and tumor homing, contributing to tumor regrowth. To study the contribution of tumor cells to tumor regrowth following therapy, we focused on tumor‐derived microparticles (TMPs). EMT/6 murine‐mammary carcinoma cells exposed to paclitaxel chemotherapy exhibited an increased number of TMPs and significantly altered their angiogenic properties. Similarly, breast cancer patients had increased levels of plasma MUC‐1⁺TMPs following chemotherapy. In addition, TMPs from cells exposed to paclitaxel induced higher BMDC mobilization and colonization, but had no increased effect on angiogenesis in Matrigel plugs and tumors than TMPs from untreated cells. Since TMPs abundantly express osteopontin, a protein known to participate in BMDC trafficking, the impact of osteopontin‐depleted TMPs on BMDC mobilization, colonization, and tumor angiogenesis was examined. Although EMT/6 tumors grown in mice inoculated with osteopontin‐depleted TMPs had lower numbers of BMDC infiltration and microvessel density when compared with EMT/6 tumors grown in mice inoculated with wild‐type TMPs, no significant difference in tumor growth was seen between the two groups. However, when BMDCs from paclitaxel‐treated mice were injected into wild‐type EMT/6‐bearing mice, a substantial increase in tumor growth and BMDC infiltration was detected compared to osteopontin‐depleted EMT/6‐bearing mice injected with BMDCs from paclitaxel‐treated mice. Collectively, our results suggest that osteopontin expressed by TMPs play an important role in BMDC mobilization and colonization of tumors, but is not sufficient to enhance the angiogenic activity in tumors.     

Spirituality and medicine

INTRODUCTION: Governing bodies for medical education recommend that spirituality and medicine be incorporated into training. AIM: To pilot a workshop on spirituality and medicine on a convenience sample of preclinical medical students and internal medicine residents and determine whether content was relevant to learners at different levels, whether preliminary evaluation was promising, and to generate hypotheses for future research. SETTING: Private medical school and university primary care internal medicine residency program, both in the Northeast. CURRICULUM DESCRIPTION: The authors designed and implemented a required 2-hour workshop for all second-year medical students and a separate required 1.5-hour workshop for all primary care internal medicine house staff. The workshops used multiple educational strategies including lecture, discussion, and role-play to address educational objectives. PROGRAM EVALUATION: Learners completed optional, anonymous pre and postworkshop surveys with six 5-point Likert-rated statements and space to cite the most useful part of the curriculum and their remaining questions. One hundred and thirty-seven learners participated and 100 completed both surveys. Medical students and residents had increased (all P< or =.002): agreement regarding the appropriateness of inquiring about spiritual and religious beliefs in the medical encounter, their perceived competence in taking a spiritual history, and their perceived knowledge of available pastoral care resources. Medical students, but not residents, had an increase in their perceived comfort in working with hospital chaplains. DISCUSSION: A brief pilot workshop on spirituality and medicine had a modest effect in improving attitudes and perceived competence of both medical students and residents.     

Long-term follow-up of endurance and safety outcomes during enzyme replacement therapy for mucopolysaccharidosis VI: Final results of three clinical studies of recombinant human N-acetylgalactosamine 4-sulfatase

The objective of this study was to evaluate the long-term clinical benefits and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome), a lysosomal storage disease. Fifty-six patients derived from 3 clinical studies were followed in open-label extension studies for a total period of 97–260 Weeks. All patients received weekly infusions of rhASB at 1 mg/kg. Efficacy was evaluated by (1) distance walked in a 12-minute walk test (12MWT) or 6-minute walk test (6MWT), (2) stairs climbed in the 3-minute stair climb (3MSC), and (3) reduction in urinary glycosaminoglycans (GAG). Safety was evaluated by compliance, adverse event (AE) reporting and adherence to treatment. Results: A significant reduction in urinary GAG (71–79%) was sustained. For the 12MWT, subjects in Phase 2 showed improvement of 255 ± 191 m (mean ± SD) at Week 144; those in Phase 3 Extension demonstrated improvement from study baseline of 183 ± 26 m (mean ±  SE) in the rhASB/rhASB group at Week 96 and from treatment baseline (Week 24) of 117 ± 25 m in the placebo/rhASB group. The Phase 1/2 6MWT and the 3MSC from Phase 2 and 3 also showed sustained improvements through the final study measurements. Compliance was 98% overall. Only 560 of 4121 reported AEs (14%) were related to treatment with only 10 of 560 (2%) described as severe. Conclusion: rhASB treatment up to 5 years results in sustained improvements in endurance and has an acceptable safety profile.