The injured heart: early cardiac effects of hematopoietic stem cell transplantation in children and young adults.

We hypothesized that subclinical cardiac injury in the peri-transplant period is more frequent than currently appreciated in children and young adults. We performed echocardiographic screening on 227 consecutive patients prior to hematopoietic stem cell transplantation (HSCT), and 7, 30 and 100 days after transplant. We measured cardiac biomarkers cardiac troponin-I (cTn-I), and soluble suppressor of tumorigenicity 2 (sST2) prior to transplant, during conditioning, and days +7, +14, +28 and +49 in 26 patients. We subsequently analyzed levels of cTn-I every 48-72 h in 15 consecutive children during conditioning. Thirty-two percent (73/227) of patients had a new abnormality on echocardiogram. New left ventricular systolic dysfunction (LVSD) occurred in 6.2% of subjects and new pericardial effusion in 27.3%. Eight of 227 (3.5%) patients underwent pericardial drain placement, and 5 (2.2%) received medical therapy for clinically occult LVSD. cTn-I was elevated in 53.0% of all samples and sST2 in 38.2%. At least one sample had a detectable cTn-I in 84.6% of patients and an elevated sST2 in 76.9%. Thirteen of fifteen patients monitored frequently during condition had elevation of cTn-I. Echocardiographic and biochemical abnormalities are frequent in the peri-HSCT period. Echocardiogram does not detect all subclinical cardiac injuries that may become clinically relevant over longer periods.

Compromise of endogenous neuropeptide W production abrogates the dipsogenic and pressor effects of angiotensin II in adult male rats.

Neuropeptide W (NPW), an endogenous ligand for the G-protein coupled receptor GPR7, is produced in neurones in the rat hypothalamus and brain stem known to be important in the control of food intake and the neuroendocrine response to stress. In previous studies, central administration of NPW during the light phase increased food and water intake and elevated prolactin and corticosterone levels in conscious, unrestrained male rats. In the present study, central administration of small-interfering RNA (siRNA) reduced NPW levels in the hypothalamus and resulted in a failure of angiotensin II to stimulate water drinking or increase mean arterial pressure. In addition, siRNA-treated animals failed to mount a significant prolactin response to immobilisation stress, at the same time as maintaining a normal corticosterone response. These results suggest that endogenous NPW may be a physiologically relevant, downstream mediator of the central actions of angiotensin II to stimulate thirst and increase arterial pressure. In addition, NPW-producing neurones appear to participate in the hypothalamic mechanisms controlling prolactin (but not corticosterone) secretion.

Using social network analysis to examine the decision-making process on new vaccine introduction in Nigeria.

The decision-making process to introduce new vaccines into national immunization programmes is often complex, involving many stakeholders who provide technical information, mobilize finance, implement programmes and garner political support. Stakeholders may have different levels of interest, knowledge and motivations to introduce new vaccines. Lack of consensus on the priority, public health value or feasibility of adding a new vaccine can delay policy decisions. Efforts to support country-level decision-making have largely focused on establishing global policies and equipping policy makers with the information to support decision-making on new vaccine introduction (NVI). Less attention has been given to understanding the interactions of policy actors and how the distribution of influence affects the policy process and decision-making. Social network analysis (SNA) is a social science technique concerned with explaining social phenomena using the structural and relational features of the network of actors involved. This approach can be used to identify how information is exchanged and who is included or excluded from the process. For this SNA of vaccine decision-making in Nigeria, we interviewed federal and state-level government officials, officers of bilateral and multilateral partner organizations, and other stakeholders such as health providers and the media. Using data culled from those interviews, we performed an SNA in order to map formal and informal relationships and the distribution of influence among vaccine decision-makers, as well as to explore linkages and pathways to stakeholders who can influence critical decisions in the policy process. Our findings indicate a relatively robust engagement of key stakeholders in Nigeria. We hypothesized that economic stakeholders and implementers would be important to ensure sustainable financing and strengthen programme implementation, but some economic and implementation stakeholders did not appear centrally on the map; this may suggest a need to strengthen the decision-making processes by engaging these stakeholders more centrally and earlier.

Effects of long-term, free-air ozone fumigation on the cytokinin content of mature beech trees.

We present the results of a study of the effects of chronic exposure to elevated ozone on the cytokinins of mature beech trees. Methods for analysing the cytokinin (CK) content of beech (FAGUS SYLVATICA) were developed using seven enzyme-linked immunosorbent assays (ELISAs). Samples taken during 2003 and 2004 from 10 mature beech trees in Kranzberg forest, 5 trees exposed to twice ambient ozone (2 x O(3)) by free-air fumigation and 5 control trees (1 x O(3)), were analysed. In 2003 and 2004 the cytokinin content of leaf samples followed a similar seasonal pattern. In leaf samples, the content of aromatic types was equal to that of the isoprenoid types. In root samples, the level of aromatic types was no different from leaves, but that of the isoprenoid types was much higher. Leaf and phloem cytokinin contents for 2 x O(3) trees were lower than for 1 x O(3) at almost all sampling times. The effect of ozone was greater for leaves in the sun crown than for leaves in the shade crown. By contrast, the root and xylem contents of cytokinin for 2 x O(3) trees were greatly elevated over the values for 1 x O(3) trees early in the growing season. We propose that O(3)-associated CK destruction in leaves reduces CK-mediated root growth suppression. The resulting increases in root growth and ectomycorrhiza, reported by other groups in the Kranzberg forest project, are likely to be responsible for the increased CK export in xylem, although O(3)-associated CK destruction in the leaves appears to nullify this increase.

Effects of perinatal thyroid hormone deprivation on the growth and behaviour of newborn mice.

Experiments were designed to distinguish between neonatal effects due to maternal thyroxine (T4) deprivation and those due to autonomous (fetus/pup) T4 deprivation, employing mice heterozygous for the bTG-tk transgene TG66,19 which specifically directs high-level expression of herpes virus type I thymidine kinase to the thyrocytes. Heterozygous TG66.19 females were either untreated or Ganciclovir was administered to destroy their thyrocytes and so render them T4-deficient. When mated to normal males these heterozygous females are expected to produce on average 50% normal and 50% heterozygous transgenic conceptuses. Ganciclovir was administered to the dams (both untreated and Ganciclovir-pretreated) during days 14-18 of gestation. At optimum levels of in utero Ganciclovir administration the non-transgenic pups showed no discernible effect while the transgenic pups were rendered athyrocytic and completely T4-deficient. The dams pretreated with Ganciclovir are hypothyroid throughout gestation, while the dams to which Ganciclovir was administered for the first time during gestation are not expected to become hypothyroid until about the time of parturition. In this way four sets of pups were generated for purposes of comparison: hypothyroid (transgenic) and euthyroid (non-transgenic) pups born to euthyroid dams and hypothyroid and euthyroid pups born to hypothyroid (Ganciclovir-pretreated) dams. Normal growth during days 1-10 after birth was dominated by the T4 status of the dam during gestation. Growth during days 11-21 and the correct timing of eye opening and ear elevation were dominated by the autonomous T4 status of the fetus/pup. The timely development of the surface-righting reflex (relative to weight gain) was shown to require both maternal and fetus/pup T4. The development of the cliff-avoidance reflex was independent of the T4 status of both pup and dam and of pup weight. The size of the pups at birth depended primarily on a normal T4 status in the dam but surprisingly T4 deficiency in fetuses/pups partly compensated for maternal T4 deficiency. The results presented here clearly demonstrate the utility of the HSV-tk-transgene-Ganciclovir-administration protocol in studying the interplay of maternal and fetal T4 deprivation in rodents.