Search

Abstract Background The achievement of the Millennium Development Goals (MDGs) depends on sufficient supply of health workforce in each country. Although country-level data support this contention, it has been difficult to evaluate health workforce supply and MDG outcomes at the country level. The purpose of the study was to examine the association between the health workforce, particularly the nursing workforce, and the achievement of the MDGs, taking into account other factors known to influence health status, such as socioeconomic indicators. Methods A merged data set that includes country-level MDG outcomes, workforce statistics, and general socioeconomic indicators was utilized for the present study. Data were obtained from the Global Human Resources for Health Atlas 2004, the WHO Statistical Information System (WHOSIS) 2000, UN Fund for Development and Population Assistance (UNFDPA) 2000, the International Council of Nurses "Nursing in the World", and the WHO/UNAIDS database. Results The main factors in understanding HIV/AIDS prevalence rates are physician density followed by female literacy rates and nursing density in the country. Using general linear model approaches, increased physician and nurse density (number of physicians or nurses per population) was associated with lower adult HIV/AIDS prevalence rate, even when controlling for socioeconomic indicators. Conclusion Increased nurse and physician density are associated with improved health outcomes, suggesting that countries aiming to attain the MDGs related to HIV/AIDS would do well to invest in their health workforce. Implications for international and country level policy are discussed.

Abstract Background The purpose of this research is to understand the performance of home healthcare practice in the US. The relationships between home healthcare patient factors and agency characteristics are not well understood. In particular, discharge destination and length of stay have not been studied using a data mining approach which may provide insights not obtained through traditional statistical analyses. Methods The data were obtained from the 2000 National Home and Hospice Care Survey data for three specific conditions (chronic obstructive pulmonary disease, heart failure and hip replacement), representing nearly 580 patients from across the US. The data mining approach used was CART (Classification and Regression Trees). Our aim was twofold: 1) determining the drivers of home healthcare service outcomes (discharge destination and length of stay) and 2) examining the applicability of induction through data mining to home healthcare data. Results Patient age (85 and older) was a driving force in discharge destination and length of stay for all three conditions. There were also impacts from the type of agency, type of payment, and ethnicity. Conclusion Patients over 85 years of age experience differential outcomes depending on the condition. There are also differential effects related to agency type by condition although length of stay was generally lower for hospital-based agencies. The CART procedure was sufficiently accurate in correctly classifying patients in all three conditions which suggests continuing utility in home health care.

[11C]befloxatone is a high-affinity, reversible, and selective radioligand for the in vivo visualization of the monoamine oxidase A (MAO-A) binding sites using positron emission tomography (PET). The multi-injection approach was used to study in baboons the interactions between the MAO-A binding sites and [11C]befloxatone. The model included four compartments and seven parameters. The arterial plasma concentration, corrected for metabolites, was used as input function. The experimental protocol—three injections of labeled and/or unlabeled befloxatone—allowed the evaluation of all the model parameters from a single PET experiment. In particular, the brain regional concentrations of the MAO-A binding sites (B′max) and the apparent in vivo befloxatone affinity (Kd) were estimated in vivo for the first time. A high binding site density was found in almost all the brain structures (170±39 and 194±26 pmol/mL in the frontal cortex and striata, respectively, n=5). The cerebellum presented the lowest binding site density (66±13 pmol/mL). Apparent affinity was found to be similar in all structures (KdVR=6.4±1.5 nmol/L). This study is the first PET-based estimation of the Bmax of an enzyme. [ABSTRACT FROM AUTHOR]

[11C]SL-25.1188 [(S)-5-methoxymethyl-3-[6-(4,4,4-trifluorobutoxy)-benzo[ d]isoxazol-3-yl]-oxazolidin-2-one], an oxazolidinone derivative, was characterized in baboons as a radioligand for the in vivo visualization of MAO-B using positron emission tomography (PET). After i.v. injection, [11C]SL25.1188 presented a rapid phase of distribution in blood (about 5 min), followed by a T1/2 elimination of 85 ± 14 min. Plasma metabolism analysis showed that [11C]SL25.1188 is stable in vivo at least for 30 min. Brain uptake was rapid with the highest one observed in the striatum and thalamus, and the lowest in the pons. Calculated distribution volumes ( VT) were as follows: striatum = 10.3, thalamus = 10.9, hippocampus = 8.9, temporal cortex = 7.7, occipital cortex = 7.2, parietal cortex = 7.4, frontal cortex = 7.4, white matter = 7.4, and pons = 6.1. Pretreatment with deprenyl (2 mg/kg, i.v.) or lazabemide (0.5 mg/kg, i.v.) reduced VT values in all brain areas up to 50%. In displacement experiments, injection of SL25.1188 or deprenyl (1 and 2 mg/kg, i.v., respectively) strongly reduced the specific uptake of [11C]SL25.1188 in all brain areas (85-100%), while a lesser displacement was observed with lazabemide (0.5 mg/kg, i.v.) (55-70% of specific binding depending on the brain area). Therefore, [11C]SL25.1188 is characterized in vivo by reversible binding, high brain uptake and very slow plasma metabolism, strongly suggesting that this radioligand is a potent tool for the in vivo study of brain MAO-B. Synapse 64:61-69, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

In this paper, we report on the pharmacological and functional profile of SSR180711 (1,4-Diazabicyclo[3.2.2]nonane-4-carboxylic acid, 4-bromophenyl ester), a new selective α7 acetylcholine nicotinic receptor (n-AChRs) partial agonist. SSR180711 displays high affinity for rat and human α7 n-AChRs (Ki of 22±4 and 14±1 nM, respectively). Ex vivo 3[H]α-bungarotoxin binding experiments demonstrate that SSR180711 rapidly penetrates into the brain (ID50=8 mg/kg p.o.). In functional studies performed with human α7 n-AChRs expressed in Xenopus oocytes or GH4C1 cells, the compound shows partial agonist effects (intrinsic activity=51 and 36%, EC50=4.4 and 0.9 μM, respectively). In rat cultured hippocampal neurons, SSR180711 induced large GABA-mediated inhibitory postsynaptic currents and small α-bungarotoxin sensitive currents through the activation of presynaptic and somato-dendritic α7 n-AChRs, respectively. In mouse hippocampal slices, the compound increased the amplitude of both glutamatergic (EPSCs) and GABAergic (IPSCs) postsynaptic currents evoked in CA1 pyramidal cells. In rat and mouse hippocampal slices, a concentration of 0.3 μM of SSR180711 increased long-term potentiation (LTP) in the CA1 field. Null mutation of the α7 n-AChR gene totally abolished SSR180711-induced modulation of EPSCs, IPSCs and LTP in mice. Intravenous administration of SSR180711 strongly increased the firing rate of single ventral pallidum neurons, extracellularly recorded in anesthetized rats. In microdialysis experiments, administration of the compound (3–10 mg/kg i.p.) dose-dependently increased extracellular acetylcholine (ACh) levels in the hippocampus and prefrontal cortex of freely moving rats. Together, these results demonstrate that SSR180711 is a selective and partial agonist at human, rat and mouse α7 n-AChRs, increasing glutamatergic neurotransmission, ACh release and LTP in the hippocampus.Neuropsychopharmacology (2007) 32, 1–16. doi:10.1038/sj.npp.1301189; published online 4 October 2006 [ABSTRACT FROM AUTHOR]

Befloxatone (1, (5R)-5-(methoxymethyl)-3-[4-[(3R)-4,4,4-trifluoro-3-hydroxybutoxy]phenyl]-2-oxazolidinone) is an oxazolidinone derivative belonging to a new generation of reversible and selective mono-amine oxidase-A (MAO-A) inhibitors. In vitro and ex vivo studies have demonstrated that befloxatone is a potent, reversible and competitive MAO-A inhibitor with potential antidepressant properties. Befloxatone (1) was labelled with carbon-11 (t1/2: 20.4 min) using [11C]phosgene as reagent. Typically, starting from a 1.2 Ci (44.4 GBq) cyclotron-produced [11C]CH4 batch, 150–300 mCi (5.55–11.10 GBq) of [11C]befloxatone ([11C]-1) with a radiochemical- and chemical purity of more than 99% were routinely obtained within 20 min of radiosynthesis (including HPLC purification) with specific radioactivities of 500–2000 mCi/μmol (18.5–74.0 GBq/μmol). The results obtained in vivo with carbon-11-labelled befloxatone not only confirm the biochemical and pharmacological profile of befloxatone found in rodent and in human tissues but also point out [11C]befloxatone as an excellent tool for the assessment of MAO-A binding sites using positron emission tomography, a high-resolution, sensitive, non-invasive and quantitative imaging technique. [Copyright &y& Elsevier]

In this paper, we report on the pharmacological and functional profile of SSR180711 (1,4-Diazabicyclo[3.2.2]nonane-4-carboxylic acid, 4-bromophenyl ester), a new selective alpha7 acetylcholine nicotinic receptor (n-AChRs) partial agonist. SSR180711 displays high affinity for rat and human alpha7 n-AChRs (K(i) of 22+/-4 and 14+/-1 nM, respectively). Ex vivo (3)[H]alpha-bungarotoxin binding experiments demonstrate that SSR180711 rapidly penetrates into the brain (ID(50)=8 mg/kg p.o.). In functional studies performed with human alpha7 n-AChRs expressed in Xenopus oocytes or GH4C1 cells, the compound shows partial agonist effects (intrinsic activity=51 and 36%, EC(50)=4.4 and 0.9 microM, respectively). In rat cultured hippocampal neurons, SSR180711 induced large GABA-mediated inhibitory postsynaptic currents and small alpha-bungarotoxin sensitive currents through the activation of presynaptic and somato-dendritic alpha7 n-AChRs, respectively. In mouse hippocampal slices, the compound increased the amplitude of both glutamatergic (EPSCs) and GABAergic (IPSCs) postsynaptic currents evoked in CA1 pyramidal cells. In rat and mouse hippocampal slices, a concentration of 0.3 muM of SSR180711 increased long-term potentiation (LTP) in the CA1 field. Null mutation of the alpha7 n-AChR gene totally abolished SSR180711-induced modulation of EPSCs, IPSCs and LTP in mice. Intravenous administration of SSR180711 strongly increased the firing rate of single ventral pallidum neurons, extracellularly recorded in anesthetized rats. In microdialysis experiments, administration of the compound (3-10 mg/kg i.p.) dose-dependently increased extracellular acetylcholine (ACh) levels in the hippocampus and prefrontal cortex of freely moving rats. Together, these results demonstrate that SSR180711 is a selective and partial agonist at human, rat and mouse alpha7 n-AChRs, increasing glutamatergic neurotransmission, ACh release and LTP in the hippocampus.