The potential for community health workers to improve child health in sub-Saharan Africa is not well understood. Healthy Child Uganda implemented a volunteer community health worker child health ...promotion model in rural Uganda. An impact evaluation was conducted to assess volunteer community health workers' effect on child morbidity, mortality and to calculate volunteer retention.
Two volunteer community health workers were selected, trained and promoted child health in each of 116 villages (population ∼61,000) during 2006-2009. Evaluation included a household survey of mothers at baseline and post-intervention in intervention/control areas, retrospective reviews of community health worker birth/child death reports and post-intervention focus group discussions. Retention was calculated from administrative records. Main outcomes were prevalence of recent child illness/underweight status, community health worker reports of child deaths, focus group perception of effect, and community health worker retention. After 18-36 months, 86% of trained volunteers remained active. Post-intervention surveys in intervention households revealed absolute reductions of 10.2% 95%CI (-17.7%, -2.6%) in diarrhea prevalence and 5.8% 95%CI (-11.5%, -0.003%) in fever/malaria; comparative decreases in control households were not statistically significant. Underweight prevalence was reduced by 5.1% 95%CI (-10.7%, 0.4%) in intervention households. Community health worker monthly reports revealed a relative decline of 53% in child deaths (<5 years old), during the first 18 months of intervention. Focus groups credited community health workers with decreasing child deaths, improved care-seeking practices, and new income-generating opportunities.
A low-cost child health promotion model using volunteer community health workers demonstrated decreased child morbidity, dramatic mortality trend declines and high volunteer retention. This sustainable model could be scaled-up to sub-Saharan African communities with limited resources and high child health needs.
It was long thought that astrocytes, given their lack of electrical signaling, were not involved in communication with neurons. However, we now know that one astrocyte on average maintains and ...regulates the extracellular neurotransmitter and potassium levels of more than 140,000 synapses, both excitatory and inhibitory, within their individual domains, and form a syncytium that can propagate calcium waves to affect distant cells via release of ‘gliotransmitters’ such as glutamate, ATP, or adenosine. Neuromodulators can affect signal-to-noise and frequency transmission within cortical circuits by effects on inhibition, allowing for the filtering of relevant versus irrelevant stimuli. Moreover, synchronized ‘resting’ and desynchronized ‘activated’ brain states are gated by short bursts of high-frequency neuromodulatory activity, highlighting the need for neuromodulation that is robust, rapid, and far-reaching. As many neuromodulators are released in a volume manner where degradation/uptake and the confines of the complex CNS limit diffusion distance, we ask the question – are astrocytes responsible for rapidly extending neuromodulator actions to every synapse? Neuromodulators are known to influence transitions between brain states, leading to control over plasticity, responses to salient stimuli, wakefulness, and sleep. These rapid and wide-spread state transitions demand that neuromodulators are able to simultaneously influence large and diverse regions in a manner that should be impossible given the limitations of simple diffusion. Intriguingly, astrocytes are ideally situated to amplify/extend neuromodulator effects over large populations of synapses given that each astrocyte can 1) ensheath a large number of synapses, 2) release gliotransmitters (glutamate/ATP/adenosine) known to affect inhibition, 3) regulate extracellular potassium that can affect excitability and excitation/inhibition balance, and 4) express receptors for all neuromodulators. In this review, we explore the hypothesis that astrocytes extend and amplify neuromodulatory influences on neuronal networks via alterations in calcium dynamics, the release of gliotransmitters, and potassium homeostasis. Given that neuromodulatory networks are at the core of our sleep-wake cycle and behavioral states, and determine how we interact with our environment, this review highlights the importance of basic astrocyte function in homeostasis, general cognition, and psychiatric disorders.
The LHCb RICH upgrade for the high luminosity LHC era Wotton, S.A.
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
01/2024, Letnik:
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Journal Article
Globally, health worker shortages continue to plague developing countries. Community health workers are increasingly being promoted to extend primary health care to under served populations. Since ...2004, Healthy Child Uganda (HCU) has trained volunteer community health workers in child health promotion in rural southwest Uganda. This study analyses the retention and motivation of volunteer community health workers trained by HCU. It presents retention rates over a 5-year period and provides insight into volunteer motivation. The findings are based on a 2010 retrospective review of the community health worker registry and the results of a survey on selection and motivation. The survey was comprised of qualitative and quantitative questions and verbally administered to a convenience sample of project participants. Between February 2004 and July 2009, HCU trained 404 community health workers (69% female) in 175 villages. Volunteers had an average age of 36.7 years, 4.9 children and some primary school education. Ninety-six per cent of volunteer community health workers were retained after lyear (389/404), 91% after 2years (386/404) and 86% after 5years (101/117). Of the 54 'dropouts', main reasons cited for discontinuation included 'too busy' (12), moved (11), business/employment (8), death (6) and separation/divorce (6). Of 58 questionnaire respondents, most (87%) reported having been selected at an inclusive community meeting. Pair-wise ranking was used to assess the importance of seven 'motivational factors' among respondents. Those highest ranked were 'improved child health', 'education/training' and 'being asked for advice/assistance by peers', while the modest 'transport allowance' ranked lowest. Our findings suggest that in our rural, African setting, volunteer community health workers can be retained over the medium term. Community health worker programmes should invest in community involvement in selection, quality training, supportive supervision and incentives, which may promote improved retention.
Changes in extracellular potassium (K+e) modulate neuronal networks via changes in membrane potential, voltage‐gated channel activity, and alteration to transmission at the synapse. Given the limited ...extracellular space in the central nervous system, potassium clearance is crucial. As activity‐induced potassium transients are rapidly managed by astrocytic Kir4.1 and astrocyte‐specific Na+/K+‐ATPase, any neurotransmitter/neuromodulator that can regulate their function may have indirect influence on network activity. Neuromodulators differentially affect cortical/thalamic networks to align sensory processing with differing behavioral states. Given serotonin (5HT), norepinephrine (NE), and acetylcholine (ACh) differentially affect spike frequency adaptation and signal fidelity (“signal‐to‐noise”) in somatosensory cortex, we hypothesize that K+e may be differentially regulated by the different neuromodulators to exert their individual effects on network function. This study aimed to compare effects of individually applied 5HT, NE, and ACh on regulating K+e in connection to effects on cortical‐evoked response amplitude and adaptation in male mice. Using extracellular field and K+ ion‐selective recordings of somatosensory stimulation, we found that differential effects of 5HT, NE, and ACh on K+e regulation mirrored differential effects on amplitude and adaptation. 5HT effects on transient K+ recovery, adaptation, and field post‐synaptic potential amplitude were disrupted by barium (200 µM), whereas NE and ACh effects were disrupted by ouabain (1 µM) or iodoacetate (100 µM). Considering the impact K+e can have on many network functions; it seems highly efficient that neuromodulators regulate K+e to exert their many effects. This study provides functional significance for astrocyte‐mediated buffering of K+e in neuromodulator‐mediated shaping of cortical network activity.
Differential effects of neuromodulators on evoked increases in extracellular potassium mirror differential neuromodulator effects on adaptation. Activity‐induced recovery decay tau is accelerated by 5HT and NE, but not ACh. Likewise, somatosensory adaptation is decreased by 5HT and NE, but not ACh.
In the somatosensory cortex, inhibitory networks are involved in low frequency sensory input adaptation/habituation that can be observed as a paired-pulse depression when using a dual stimulus ...electrophysiological paradigm. Given that astrocytes have been shown to regulate inhibitory interneuron activity, we hypothesized that astrocytes are involved in cortical sensory adaptation/habituation and constitute effectors of the 5HT-mediated increase in frequency transmission. Using extracellular recordings of evoked excitatory postsynaptic potentials (eEPSPs) in layer II/III of somatosensory cortex, we used various pharmacological approaches to assess the recruitment of astrocyte signaling in paired-pulse depression and serotonin-mediated increase in the paired-pulse ratio (pulse 2/pulse 1). In the absence of neuromodulators or pharmacological agents, the first eEPSP is much larger in amplitude than the second due to the recruitment of long-lasting evoked GABAA-dependent inhibitory activity from the first stimulus. Disruption of glycolysis or mGluR5 signaling resulted in a very similar loss of paired-pulse depression in field recordings. Interestingly, paired-pulse depression was similarly sensitive to disruption by ATP P2Y and adenosine A2A receptor antagonists. In addition, we show that pharmacological disruption of paired-pulse depression by mGluR5, P2Y, and glycolysis inhibition precluded serotonin effects on frequency transmission (typically increased the paired-pulse ratio). These data highlight the possibility for astrocyte involvement in cortical inhibitory activity seen in this simple cortical network and that serotonin may act on astrocytes to exert some aspects of its modulatory influence.
•The pharmacology of frequency adaptation was evaluated in mouse cortical slices.•Astrocyte directed pharmacological blockade disrupts frequency adaptation.•Purinergic P2Y or A2A receptor block disrupts frequency adaptation.•5HT effects on adaptation are lost after pharmacological disruption of astrocytes.
Both serotonin (5‐HT) and stress exert changes in cortical inhibitory tone to shape the activity of cortical networks. Because astrocytes are also known to affect inhibition through established ...purinergic pathways, we assessed the role of GABA and purinergic pathways with respect to the effects of rapid corticosterone (CORT) and 5‐HT on cortical inhibition. We used a paired‐pulse paradigm (P1 and P2) in acutely isolated mouse brain slices to evaluate changes in cortical evoked inhibition. Normally, 5‐HT decreases the amplitude of the first pulse P1, whereas it increases the amplitude of P2 (increasing frequency transmission). Interestingly, it was observed that CORT application decreased P1 and increased P2 similar to that of 5‐HT application. Given that CORT and 5‐HT are known to modulate inhibition, we applied the GABAA antagonist bicuculline in the presence of both and found that the increase in P2 and the P2/P1 was lost, providing evidence for a common mechanism involving GABAA receptor signalling. Additional occlusion experiments (ie, 5‐HT in presence of CORT and CORT in presence of 5‐HT) provide further support for a common mechanism. Because both 5‐HT and CORT blocked the increase in P2 and P2/P1 with respect to the other, we suggest 5‐HT/CORT already utilise the shared mechanism to affect cortical inhibition. Using low concentrations of the GAPDH inhibitor iodoacetate, as commonly used to selectively disrupt astrocyte metabolism, we found that the increase in P2 and P2/P1 was similarly blocked in response to both CORT and 5‐HT. Because astrocyte signalling depends in large part on purinergic pathways, the purinergic contribution was assessed using Ab129 (P2Y antagonist) and SCH 58261 (A2A antagonist). Once again, P2Y and A2A receptor blockade similarly disrupted 5‐HT‐ or CORT‐mediated increases in P2 and P2/P1. Taken together, these results support the common involvement of GABAergic and purinergic pathways in the effects of CORT and 5‐HT that may also involve astrocytes.
Lipopolysaccharide (LPS)-mediated sickness behaviour is known to be a result of increased inflammatory cytokines in the brain. Inflammatory cytokines have been shown to mediate increases in brain ...excitation by loss of GABAA-mediated inhibition through receptor internalization or inactivation. Inflammatory pathways, reactive oxygen species and stress are also known to increase monoamine oxidase-A (MAO-A) and acetylcholinesterase (ACh-E) activity. Given that neuromodulator actions on neural circuits largely depend on inhibitory pathways and are sensitive to alteration in corresponding catalytic enzyme activities, we assessed the impact of systemic LPS on neuromodulator-mediated shaping of a simple cortical network.
Extracellular field recordings of evoked postsynaptic potentials in adult mouse somatosensory cortical slices were used to evaluate effects of a single systemic LPS challenge on neuromodulator function 1 week later. Neuromodulators were administered transiently as a bolus (100 μl) to the bath perfusate immediately upstream of the recording site to mimic phasic release of neuromodulators and enable assessment of response temporal dynamics.
Systemic LPS administration resulted in loss of both spontaneous and evoked inhibition as well as alterations in the temporal dynamics of neuromodulator effects on a paired-pulse paradigm. The effects on neuromodulator temporal dynamics were sensitive to the Monoamine oxidase-A (MAO-A) antagonist clorgyline (for norepinephrine and serotonin) and the ACh-E inhibitor donepezil (for acetylcholine). This is consistent with significant increases in total MAO and ACh-E activity found in hemi-brain samples from the LPS-treated group, supporting the notion that systemic LPS administration may lead to longer-lasting changes in inhibitory network function and enzyme (MAO/ACh-E) activity responsible for reduced neuromodulator actions.
Given the significant role of neuromodulators in behavioural state and cognitive processes, it is possible that an inflammatory-mediated change in neuromodulator action plays a role in LPS-induced cognitive effects and could help define the link between infection and neuropsychiatric/degenerative conditions.
High-power (HP) light emitting diodes (LEDs) offer exciting opportunities for plant lighting research. LED technology now provides intensity levels and wavelengths potentially well suited to study ...plant growth and development under 'realistic', or specific artificially manipulated radiation environments. However, while the ability offered by LEDs to specify precisely the spectral composition provides greater flexibility than conventional broad-spectrum lighting, it also presents significant challenges in characterising what might constitute an 'optimum' light spectrum for plant growth. Plant growth and development under custom-designed HP LED arrays, capable of supporting up to 700 LEDs and as many as 10 spectral peaks, were studied within the controlled environment rooms at the New Zealand Controlled Environment Laboratory (NZCEL). White-based and red-blue (RB) based LED spectra, consisting of multitude peaks between 400 and 740 nm, were examined for their potential as sole-source lighting rigs for growing Arabidopsis thaliana. Development rates and biomass were measured from germination to seed set under 200 and 400 µmol m-2 s-1 photosynthetically active radiation (PAR), provided by HP LED arrays or the standard high pressure discharge (HID) metal halide and tungsten halogen lighting rig used within NZCEL. Development rate was comparable under the two light sources, but greater biomass obtained under LED suggests an additional potential benefit of LEDs over conventional HID lighting.
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