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Background: Many countries in middle-and low-income countries today suffer from severe staff shortages and/or maldistribution of health personnel which has been aggravated more recently by the disintegration of health systems in low-income countries and by the global policy environment. One of the most damaging effects of severely weakened and under-resourced health systems is the difficulty they face in producing, recruiting, and retaining health professionals, particularly in remote areas. Low wages, poor working conditions, lack of supervision, lack of equipment and infrastructure as well as HIV and AIDS, all contribute to the flight of health care personnel from remote areas. In this global context of accelerating inequities health service policy makers and managers are searching for ways to improve the attraction and retention of staff in remote areas. But the development of appropriate strategies first requires an understanding of the factors which influence decisions to accept and/or stay in a remote post, particularly in the context of mid and low income countries (MLICS), and which strategies to improve attraction and retention are therefore likely to be successful. It is the aim of this review article to explore the links between attraction and retention factors and strategies, with a particular focus on the organisational diversity and location of decision-making.

MicroRNAs (miRNAs) represent a new class of small non-coding RNAs regulating gene expression by inducing RNA degradation or interfering with translation. Aberrant miRNA expression has been described for several human malignancies and tumour suppressor functions have been ascribed to this new class of small regulatory RNAs. Accordingly, inactivation due to deletion or mutation has been found in human malignancies. Here, we describe the role of aberrant hypermethylation as an additional mechanism for miRNA gene inactivation in human breast cancer. Aberrant hypermethylation was shown for mir-9-1, mir-124a3, mir-148, mir-152, and mir-663 in 34-86% of cases in a series of 71 primary human breast cancer specimens. For comprehensive methylation analysis, combined bisulphite restriction analysis, bisulphite sequencing, and Pyrosequencing were employed. miRNA gene hypermethylation correlated strongly with methylation of known tumour suppressor genes (p = 0.003). After treatment of various breast cancer cell lines with the demethylating agent 5-aza-2'-deoxycytidine, reduction of mir-9-1 gene methylation and concomitant reactivation of expression could be observed. For the mir-9-1 gene, which is already hypermethylated in pre-invasive intraductal lesions, a good correlation between quantitative methylation level and reduction of expression could be demonstrated in a subset of primary human breast cancer specimen (r = 0.8). In conclusion, this study demonstrates that various microRNA genes are also affected by epigenetic inactivation due to aberrant hypermethylation and that this is an early and frequent event in breast cancer development.

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