The effects of dictatorship on health: the case of Turkmenistan

BACKGROUND: There is a health crisis in Turkmenistan similar to, but more severe than, in other Central Asian countries. This paper asks whether the health crisis in Turkmenistan is attributable to the consequences of the dictatorship under president Niyazov, who died in 2006. METHODS: The basis for this paper was a series of semi-structured in-depth interviews with key informants complemented by an iterative search of internet sites, initially published as a report in April 2005, and subsequently updated with feedback on the report as well as a comprehensive search of secondary information sources and databases. RESULTS: This paper describes in depth three areas in which the dictatorship in Turkmenistan had a negative impact on population health: the regime's policy of secrecy and denial, which sees the "solution" to health care problems in concealment rather than prevention; its complicity in the trafficking of drugs from Afghanistan; and the neglect of its health care system. CONCLUSION: The paper concludes that dictatorship has contributed to the health crisis facing Turkmenistan. One of the first tests of the new regime will be whether it can address this crisis

Rational identification of a Cdc42 inhibitor presents a new regimen for long- term hematopoietic stem cell mobilization

Mobilization of hematopoietic stem cells (HSCs) from bone marrow (BM) to peripheral blood (PB) by cytokine granulocyte colony-stimulating factor (G-CSF) or the chemical antagonist of CXCR4, AMD3100, is important in the treatment of blood diseases. Due to clinical conditions of each application, there is a need for continued improvement of HSC mobilization regimens. Previous studies have shown that genetic ablation of the Rho GTPase Cdc42 in HSCs results in their mobilization without affecting survival. Here we rationally identified a Cdc42 activity-specific inhibitor (CASIN) that can bind to Cdc42 with submicromolar affinity and competitively interfere with guanine nucleotide exchange activity. CASIN inhibits intracellular Cdc42 activity specifically and transiently to induce murine hematopoietic stem/progenitor cell egress from the BM by suppressing actin polymerization, adhesion, and directional migration of stem/progenitor cells, conferring Cdc42 knockout phenotypes. We further show that, although, CASIN administration to mice mobilizes similar number of phenotypic HSCs as AMD3100, it produces HSCs with better long-term reconstitution potential than that by AMD3100. Our work validates a specific small molecule inhibitor for Cdc42, and demonstrates that signaling molecules downstream of cytokines and chemokines, such as Cdc42, constitute a useful target for long-term stem cell mobilization

Haematopoietic stem cells in perisinusoidal niches are protected from ageing.

With ageing, intrinsic haematopoietic stem cell (HSC) activity decreases, resulting in impaired tissue homeostasis, reduced engraftment following transplantation and increased susceptibility to diseases. However, whether ageing also affects the HSC niche, and thereby impairs its capacity to support HSC function, is still widely debated. Here, by using in-vivo long-term label-retention assays we demonstrate that aged label-retaining HSCs, which are, in old mice, the most quiescent HSC subpopulation with the highest regenerative capacity and cellular polarity, reside predominantly in perisinusoidal niches. Furthermore, we demonstrate that sinusoidal niches are uniquely preserved in shape, morphology and number on ageing. Finally, we show that myeloablative chemotherapy can selectively disrupt aged sinusoidal niches in the long term, which is linked to the lack of recovery of endothelial Jag2 at sinusoids. Overall, our data characterize the functional alterations of the aged HSC niche and unveil that perisinusoidal niches are uniquely preserved and thereby protect HSCs from ageing

Assessment of young and aged hematopoietic stem cell activity by competitive serial transplantation assays

Healthy hematopoietic stem cells (HSCs) are capable to self-renew and reconstitute the complete hematopoietic system. Upon aging, there is an increased incidence of blood-related diseases. Age-related phenotypes have been widely studied by bone marrow transplantation experiments, where reconstitution of the transplanted cells is a direct measure of HSC activity. In this protocol we describe a competitive bone marrow transplantation assay to functionally test young and old HSCs

The dynamics of epidural and opioid analgesia during labour

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch)Purpose: To investigate the association of analgesia, opioids or epidural, or the combination of both with labour duration and spontaneous birth in nulliparous women. Methods: A secondary data analysis of an existing cohort study was performed and included nulliparous women (n = 2074). Durations of total labour and first and second labour stage were calculated with Kaplan-Meier estimation for the four different study groups: no analgesia (n = 620), opioid analgesia (n = 743), epidural analgesia (n = 482), and combined application (n = 229). Labour duration was compared by Cox regression while adjusting for confounders and censoring for operative births. Logistic regression was used to investigate the association between the administration of different types of analgesia and mode of birth. Results: Most women in the combined application group were first to receive opioid analgesia. Women with no analgesia had the shortest duration of labour (log rank p < 0.001) and highest chance of a spontaneous birth (p < 0.001). If analgesia was administered, women with opioids had a shorter first stage (p = 0.018), compared to women with epidural (p < 0.001) or women with combined application (p < 0.001). Women with opioids had an increased chance to reach full cervical dilatation (p = 0.006). Women with epidural analgesia (p < 0.001) and women with combined application (p < 0.001) had a prolonged second stage and decreased chance of spontaneous birth compared to women without analgesia. Conclusions: Women with opioids had a prolonged first stage, but increased chance to reach full cervical dilatation. Women with epidural analgesia and women with both opioid and epidural analgesia had a prolonged first and second stage and a decreased chance of a spontaneous birth