The Health Systems Funding Platform : is this where we thought we were going?

Background: In March 2009, the Task Force for Innovative International Financing for Health Systems recommended "a health systems funding platform for the Global Fund, GAVI Alliance, the World Bank and others to coordinate, mobilize, streamline and channel the flow of existing and new international resources to support national health strategies." Momentum to establish the Health Systems Funding Platform was swift, with the World Bank convening a Technical Workshop on Health Systems Strengthening (HSS), and serial meetings organized to progress the agenda. Despite its potential significance, there has been little comment in peer-reviewed literature, though some disquiet in the international development community around the scope of the Platform and the capacity of the partners, which appears disproportionate to the available information. Methods: This case study uses documentary analysis, participant observation and 24 in-depth interviews to examine the processes of development and key issues raised by the Platform. Results: The findings show a fluid and volatile process, with debate over whether ongoing engagement in HSS by Global Fund and GAVI represents a dilution of organizational focus, risking ongoing support, or a paradigm shift that facilitates the achievement of targeted objectives, builds systems capacity, and will attract additional resources. Uncertainty in the development of the Platform reflects the flexibility of the recently formed global health initiatives, and the instability of donor commitments, particularly in the current financial climate. But implicit in the conflict is tension between key global stakeholders over defining and ownership of the health systems agenda. Conclusions: The tensions appear to have been resolved through a focus on national planning, applying International Health Partnership principles, though the global financial crisis and key personnel changes may yet alter outcomes. Despite its dynamic evolution, the Platform may offer an incremental path towards increasing integration around health systems, that has not been previously possible

Biofluid Markers for Prodromal Parkinson's Disease:Evidence From a Catecholaminergic Perspective

Parkinson's disease (PD) is the most frequent of all Lewy body diseases, a family of progressive neurodegenerative disorders characterized by intra-neuronal cytoplasmic inclusions of α-synuclein. Its most defining features are bradykinesia, tremor, rigidity and postural instability. By the time PD manifests with motor signs, 70% of dopaminergic midbrain neurons are lost, and the disease is already in the middle or late stage. However, there are various non-motor symptoms occurring up to 20 years before the actual parkinsonism that are closely associated with profound deficiency of myocardial noradrenaline content and peripheral sympathetic denervation, as evidenced by neuroimaging experiments in recent years. Additionally, there is an inherent autotoxicity of catecholamines in the neuronal cells in which they are produced, forming toxic catecholaldehyde intermediates that make α-synuclein prone to aggregation, initiating a cascade of events that ultimately leads to neuronal death. The etiopathogenesis of PD and related synucleinopathies thus may well be a prototypical example of a catecholamine-regulated neurodegeneration, given that the synucleinopathy in PD spreads in synergy with central and peripheral catecholaminergic dysfunction from the earliest phases onward. That is why catecholamines and their metabolites, precursors, or derivatives in cerebrospinal fluid or plasma could be of particular interest as biomarkers for prodromal and de novo PD. Because there is great demand for such markers, this mini-review summarizes all catecholamine-related studies to date, in addition to providing profound neurochemical evidence on a systemic and cellular level to further emphasize this hypothesis and with emphasis on extracellular vesicles as a novel diagnostic and therapeutic incentive

SCIENTIFIC METHOD ONPRODUCTION PROCESS ASANEFFORTTOIMPROVE REAL SECTORS CONTRIBUTION TO THE INDONESIAN ECONOMY

Economic condition of Indonesia at presents, requires a positive contribution from all economic perpetrators in Indonesia, especially from real sectors. This sector becomes important because most company assets invested in this real sector activity, as well as the number of human resources. With this condition, this research aims at analyzing the application of scientific production method in real sector production activity, so that obtain information how far production activity conducted with scientific method, and how perpetrators concerned with this matter. This research was conducted with real sector as the sample in Depok and Bogor region. Analysis was done using descriptive and inferential analyses dealing with the data of the questionnaires administered. Temporary result shows that most respondents, although getting support from management (36%), the practice shows that not all respondents applied scientific production method in their production activity. Consequently, the production is not optimum. The cause was that technological aspect were not adequate due to the support of the management could not be fully realized. For example, less development time allocation and less supply of production technology infrastructure. In conclusion, this is quiet irony because real sectors are expected to have a positive contribution to the development of Indonesian economy, while the real condition of real sectors does not apply scientific method optimally yet

The monoaminergic footprint of depression and psychosis in dementia with Lewy bodies compared to Alzheimer's disease

Introduction: Depression and psychosis are two of the most severe neuropsychiatric symptoms (NPS) in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Both NPS have negative effects on cognitive performance and life expectancy. The current study aimed to investigate and compare monoaminergic etiologies between both neurodegenerative conditions, given the lack of an efficient pharmacological treatment until present.Methods: Eleven behaviorally relevant brain regions of the left frozen hemisphere of 10 neuropathologically confirmed AD patients with/without depression (AD + D/-D; 5 were psychotic within AD + D), 10 confirmed DLB patients, all of whom were depressed (DLB + D; 5 psychotic patients), and, finally, 10 confirmed control subjects were regionally dissected. All patients were retrospectively assessed before death using the Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) and Cornell Scale for Depression in Dementia amongst others. The concentrations of dopamine (DA), serotonin (5-HT), (nor) adrenaline and respective metabolites, i.e. 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), 5-hydroxy-3-indoleacetic acid (5-HIAA), and, 3-methoxy-4-hydroxyphenylglycol (MHPG), were determined using reversed-phase high-performance liquid chromatography with electrochemical detection.Results: DLB subjects had the overall lowest monoamine and metabolite concentrations regarding 33 out of 41 significant monoaminergic group alterations. Moreover, MHPG levels were significantly decreased in almost 8 out of 11 brain regions of DLB-compared to AD patients. We also observed the lowest 5-HT and 5-HIAA levels, and 5-HIAA/5-HT turnover ratios in DLB + D compared to AD + D subjects. Additionally, a 4- and 7-fold increase of DOPAC/DA and HVA/DA turnover ratios, and, a 10-fold decrease of thalamic DA levels in DLB + D compared to AD + D patients and control subjects was noticed. Regarding psychosis, hippocampal DA levels in the overall DLB group significantly correlated with Behave-AD AB scores. In the total AD group, DA levels and HVA/DA ratios in the amygdala significantly correlated with Behave-AD AB scores instead.Conclusions: Monoaminergic neurotransmitter alterations contribute differently to the pathophysiology of depression and psychosis in DLB as opposed to AD, with a severely decreased serotonergic neurotransmission as the main monoaminergic etiology of depression in DLB. Similarly, psychosis in DLB might, in part, be etiologically explained by dopaminergic alterations in the hippocampus, whereas in AD, the amygdala might be involved.</p

Sediment grain size determines microplastic exposure landscapes for sandy beach macroinfauna

Despite the global occurrence of microplastic contamination on sandy beaches, evidence of microplastic distribution within beaches remains contradictory. When conflicting evidence is used to inform sampling surveys, it increases uncertainty in resulting data. Moreover, it hampers spatially explicit risk characterization of microplastic pollution to intertidal fauna. We aimed to guide sampling designs for microplastic monitoring on beaches, and to quantify macroinfauna exposure to microplastics. Microplastic abundance, quantified between 5 mm–66 μm, lacked a significant zonation across the top sediment layer of sub-terrestrial, upper and lower midlittoral, and swash zones at two sites with varying anthropogenic influence on a microtidal dissipative beach in Uruguay. Microplastic abundance decreased exponentially with increasing grain size, as revealed by Bayesian Poisson regression, although the decrease was less steep compared to prior knowledge regarding sediment – plastic interactions obtained for large (millimeter-sized) industrial pellets. Significant differences in microplastic contamination between the two sites with varying anthropogenic influence likely related to their proximity to a freshwater canal. Corresponding field measurements of body burdens of fibers and irregular particles were significantly lower for the polychaete Euzonus (Thoracophelia) furcifera, despite its preference for finer sediments with higher microplastic loads, compared to the isopods Excirolana braziliensis and Excirolana armata. Results provide critical insights toward representative sampling of microplastics within beach sites. Specifically, we caution against sampling limited to the drift line, and instead recommend: 1) reporting beach morphodynamic characteristics; 2) using clearly defined, ecologically-informed zonation schemes; and 3) accounting for sediment grain size as a covariate to normalize among reported contamination levels. The results contribute valuable baseline data toward realistic exposure landscapes relative to the sediment grain size preferences of macroinfauna, needed to inform laboratory experiments

Cerebrospinal fluid and serum MHPG improve Alzheimer's disease versus dementia with Lewy bodies differential diagnosis

Introduction: Given the challenges concerning the differential diagnosis of dementia, we investigated the possible added value of monoaminergic compounds to the standard cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers. Particularly, regarding the AD versus dementia with Lewy bodies (DLB) comparison, monoamines or their metabolites might have added discriminative value as there is a more severe neuropathological burden in the locus coeruleus of DLB patients, the principal site of noradrenaline synthesis. Methods: We applied enzyme-linked immunosorbent assay (ELISA) to analyze CSF amyloid β peptide of 42 amino acids, total tau, and tau phosphorylated at threonine 181, in patients with AD, frontotemporal dementia, DLB/Parkinson's disease dementia, and controls. Reversed-phase high-performance liquid chromatography with electrochemical detection was implemented to study monoamine and metabolite levels in CSF and serum. Stepwise forward conditional logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic accuracy of these newly fitted models containing the most discriminative indicators of disease status. Results: Most significant differences in CSF and serum were confined to the noradrenergic system. More specifically, CSF 3-methoxy-4-hydroxyphenylglycol (MHPG) levels were higher, whereas serum MHPG levels were lower, in DLB patients compared with all other groups. Addition of CSF and serum MHPG levels to the CSF AD biomarker panel significantly increased diagnostic accuracy between DLB/Parkinson's disease dementia and AD. Interestingly, a model only including CSF and serum MHPG without the classic AD biomarker panel reached similar area under the curve values. Discussion: We hypothesize that varying degrees of neuronal loss in the locus coeruleus of DLB/Parkinson's disease dementia versus AD patients result in differentially altered MHPG levels, making this metabolite a valuable biomarker