Parathyroid hormone-related protein (PTHrP) is synthesized by diverse tissues, and its processing produces several fragments, each with apparently distinct autocrine and paracrine bioactivities. In bone, PTHrP appears to modulate bone formation in part through promoting osteoblast differentiation. The putative effect of PTH-like and PTH-unrelated fragments of PTHrP on human mesenchymal stem cell (MSCs) is not well known. Human MSCs were treated with PTHrP (1-36) or PTHrP (107-139) or both (each at 10 nM) in osteogenic or adipogenic medium, from the start or after 6 days of exposure to the corresponding medium, and the expression of several osteoblastogenic and adipogenic markers was analyzed. PTHrP (1-36) inhibited adipogenesis in MSCs and favoured the expression of osteogenic early markers. The opposite was observed with treatment of MSCs with PTHrP (107-139). Moreover, inhibition of the adipogenic differentiation by PTHrP (1-36) prevailed in the presence of PTHrP (107-139). The PTH/PTHrP type 1 receptor (PTH1R) gene expression was maximum in the earlier and later stages of osteogenesis and adipogenesis, respectively. While PTHrP (107-139) did not modify the PTH1R overexpression during adipogenesis, PTHrP (1-36) did inhibit it; an effect which was partially affected by PTHrP (7-34), a PTH1R antagonist, at 1 microM. These findings demonstrate that both PTHrP domains can exert varying effects on human MSCs differentiation. PTHrP (107-139) showed a tendency to favor adipogenesis, while PTHrP (1-36) induced a mild osteogenic effect in these cells, and inhibited their adipocytic commitment. This further supports the potential anabolic action of the latter peptide in humans.
Adipogenesis/drug effects ; Alkaline Phosphatase/biosynthesis/genetics ; Antigens, Differentiation/biosynthesis/genetics ; Bone Marrow/pathology ; Cell Differentiation/drug effects ; Cells, Cultured ; Core Binding Factor Alpha 1 Subunit/biosynthesis/genetics ; Culture Media ; Gene Expression Regulation ; Humans ; Lipoprotein Lipase/biosynthesis/genetics ; Mesenchymal Stem Cells/*drug effects/metabolism/pathology ; Osteoblasts/drug effects/*metabolism/pathology ; Osteogenesis/drug effects ; PPAR gamma/biosynthesis/genetics ; Parathyroid Hormone/*pharmacology ; Peptide Fragments/*pharmacology ; Receptor, Parathyroid Hormone, Type 1/antagonists & inhibitors

BACKGROUND: Health risk assessments (HRA) are used by many organisations as a basis for developing relevant and targeted employee health and well-being interventions. However, many HRA's have a western-centric focus and therefore it is unclear whether the results can be directly extrapolated to those from non-western countries. More information regarding the differences in the associations between country status and health risks is needed along with a more global perspective of employee health risk factors and well-being overall. Therefore we aimed to i) quantify and compare associations for a number of health risk factors based on country status, and then ii) explore which characteristics can aid better prediction of well-being levels and in turn workplace productivity globally. METHODS: Online employee HRA data collected from 254 multi-national companies, for the years 2013 through 2016 was analysed (n = 117,274). Multiple linear regression models were fitted, adjusting for age and gender, to quantify associations between country status and health risk factors. Separate regression models were used to assess the prediction of well-being measures related to productivity. RESULTS: On average, the developing countries were comprised of younger individuals with lower obesity rates and markedly higher job satisfaction compared to their developed country counterparts. However, they also reported higher levels of anxiety and depression, a greater number of health risks and lower job effectiveness. Assessment of key factors related to productivity found that region of residency was the biggest predictor of presenteeism and poor pain management was the biggest predictor of absenteeism. CONCLUSIONS: Clear differences in health risks exist between employees from developed and developing countries and these should be considered when addressing well-being and productivity in the global workforce. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40557-017-0172-1) contains supplementary material, which is available to authorized users.
Absenteeism ; Anxiety ; Depression ; Developed Countries ; Developing Countries ; Efficiency ; Internship and Residency ; Job Satisfaction ; Linear Models ; Obesity ; Occupational Health* ; Pain Management ; Presenteeism ; Risk Assessment ; Risk Factors ; Work Performance*

Chronic limb-threatening ischemia is rarely associated with previous traumatic injury. We present a case of a 28-year-old male with progressive digit ulcers, a weak pulse, cyanosis, and a cold limb. Eight months prior, he had a motorcycle accident resulting in a right clavicle fracture and brachial plexus injury. Computed tomography angiography revealed occlusion of the right subclavian artery near a surgically implanted reduction plate. The patient underwent an open subclavianbrachial bypass with a reversed saphenous vein graft. His postoperative recovery was uneventful. After 3 months, he had a euthermic right hand with a palpable pulse and his ulcers had completely healed. This case reinforces the need for patients with a neurological deficit in the upper extremity caused by blunt trauma to undergo thorough vascular examination to identify potential arterial injury and compromised perfusion.