Exposure to chronic stress is frequently accompanied by cognitive and affective disorders in association with neurostructural adaptations. Chronic stress was previously shown to trigger Alzheimer's-like neuropathology, which is characterized by Tau hyperphosphorylation and missorting into dendritic spines followed by memory deficits. Here, we demonstrate that stress-driven hippocampal deficits in wild-type mice are accompanied by synaptic missorting of Tau and enhanced Fyn/GluN2B-driven synaptic signaling. In contrast, mice lacking Tau [Tau knockout (Tau-KO) mice] do not exhibit stress-induced pathological behaviors and atrophy of hippocampal dendrites or deficits of hippocampal connectivity. These findings implicate Tau as an essential mediator of the adverse effects of stress on brain structure and function.Tau | stress | hippocampus | depression | memory deficits T he cytoskeletal protein Tau is implicated in the establishment of Alzheimer's disease (AD) (1) as well as excitotoxicity (1) and, more recently, epilepsy (2, 3). Exposure to stressful conditions induces depressive behavior and memory deficits in both rodents and humans (4-8). Studies in rodents have shown that chronic stress triggers Tau hyperphosphorylation, a key pathogenic mechanism in AD, and results in cognitive and mood deficits (9-13); however, those studies do not provide direct evidence for a role of Tau in stress-evoked brain pathology. Given that Tau plays an important role in regulating neuronal architecture and function through its interaction with various cellular targets (e.g., tubulin and Fyn) (14), we hypothesized that Tau mediates the deleterious actions of stress on brain structure and function.To test the above hypothesis, we compared the impact of chronic unpredictable stress (CUS) (11, 15) in mice carrying a null mutation of the mapt gene [Tau knockout (Tau-KO) mice] (16) with their wild-type (WT) littermates. Three well-characterized behavioral endpoints (cognition, coping styles, and anxiety) that are disrupted by CUS served as the primary assay endpoints; these were complemented with measures of hippocampal structural and functional integrity. The hippocampus is a central component of the neurocircuitries that control these behaviors and displays overt lesions in both stress-and Tau-related pathologies; in the latter, the hippocampus is one of the earliest brain regions to show signs of neurodegeneration (1,4,7,(10)(11)(12)(13)17). ResultsDeleterious Effects of Stress on Memory and Mood Are Abrogated in the Absence of Tau Protein. Cognition, mood, and anxiety are interdependent behavioral domains that exhibit complex interactions (5). Different forms of memory were assessed after exposure of WT and Tau-KO mice to the CUS paradigm; the test battery included the Y-maze, Morris water maze (MWM), and the novel object recognition test (NOR). Anxiety was evaluated using the elevated plus maze (EPM), and coping styles and anhedonia were assessed using the forced swim test (FST) and the sucrose consumption test (SCT).Two-way ANOVA ...
BackgroundPostpartum maternal and infant mortality is high in sub-Saharan Africa and improving postpartum care as a strategy to enhance maternal and infant health has been neglected. We describe the design and selection of suitable, context-specific interventions that have the potential to improve postpartum care.MethodsThe study is implemented in rural districts in Burkina Faso, Kenya, Malawi and Mozambique.We used the four steps ‘systems thinking’ approach to design and select interventions: 1) we conducted a stakeholder analysis to identify and convene stakeholders; 2) we organised stakeholders causal analysis workshops in which the local postpartum situation and challenges and possible interventions were discussed; 3) based on comprehensive needs assessment findings, inputs from the stakeholders and existing knowledge regarding good postpartum care, a list of potential interventions was designed, and; 4) the stakeholders selected and agreed upon final context-specific intervention packages to be implemented to improve postpartum care.ResultsNeeds assessment findings showed that in all study countries maternal, newborn and child health is a national priority but specific policies for postpartum care are weak and there is very little evidence of effective postpartum care implementation. In the study districts few women received postpartum care during the first week after childbirth (25 % in Burkina Faso, 33 % in Kenya, 41 % in Malawi, 40 % in Mozambique). Based on these findings the interventions selected by stakeholders mainly focused on increasing the availability and provision of postpartum services and improving the quality of postpartum care through strengthening postpartum services and care at facility and community level. This includes the introduction of postpartum home visits, strengthening postpartum outreach services, integration of postpartum services for the mother in child immunisation clinics, distribution of postpartum care guidelines among health workers and upgrading postpartum care knowledge and skills through training.ConclusionThere are extensive gaps in availability and provision of postpartum care for mothers and infants. Acknowledging these gaps and involving relevant stakeholders are important to design and select sustainable, context-specific packages of interventions to improve postpartum care.
Quantitative interpretation of time‐lapse seismic data requires knowledge of the relationship between elastic wave velocities and fluid saturation. This relationship is not unique but depends on the spatial distribution of the fluid in the pore‐space of the rock. In turn, the fluid distribution depends on the injection rate. To study this dependency, forced imbibition experiments with variable injection rates have been performed on an air‐dry limestone sample. Water was injected into a cylindrical sample and was monitored by X‐Ray Computed Tomography and ultrasonic time‐of‐flight measurements across the sample. The measurements show that the P‐wave velocity decreases well before the saturation front approaches the ultrasonic raypath. This decrease is followed by an increase as the saturation front crosses the raypath. The observed patterns of the acoustic response and water saturation as functions of the injection rate are consistent with previous observations on sandstone. The results confirm that the injection rate has significant influence on fluid distribution and the corresponding acoustic response. The complexity of the acoustic response —‐ that is not monotonic with changes in saturation, and which at the same saturation varies between hydrostatic conditions and states of dynamic fluid flow – may have implications for the interpretation of time‐lapse seismic responses.
Waves in patchy-saturated rocks are attenuated through the mechanism of wave-induced pressure diffusion. Previous studies reveal that attenuation and phase-velocity dispersion depend on the fluid patch size and distribution. These patch characteristics in turn can be influenced by capillary forces. The effect of capillarity on wave attenuation in patchy-saturated rocks is not fully understood. We studied the combined effects of wave-induced pressure diffusion and capillarity on acoustic signatures. To do so we made use of the concept of patch membrane stiffness as a macroscopic expression of capillarity. We incorporated the membrane stiffness into the continuous random media model of patchy saturation. The membrane stiffness is associated with a pressure discontinuity at patch interfaces. This pressure discontinuity impedes wave-induced pressure diffusion and, therefore, reduces wave attenuation. Conversely, the phase velocity increases due to additional capillarity reinforcement. We applied this capillarity-extended random media model to interpret velocity-saturation relations (VSR) and attenuation-saturation relations (ASR) retrieved from an ultrasonically monitored core flooding experiment. Because the fluid distribution is approximately known from accompanying computerized tomographic images, all but one required model input parameters can be inferred. The elusive input parameter is a shape factor quantifying the geometric irregularity of the pore channels. We found, however, that the experimental data can be consistently modeled only if the capillarity effect is accounted for. The results suggested that wave-induced fluid-pressure diffusion at mesoscopic patches in conjunction with capillary action can have important implications for interpreting ultrasonic VSR and ASR in patchy-saturated rocks.
Tau protein in dendrites and synapses has been recently implicated in synaptic degeneration and neuronal malfunction. Chronic stress, a well-known inducer of neuronal/synaptic atrophy, triggers hyperphosphorylation of Tau protein and cognitive deficits. However, the cause-effect relationship between these events remains to be established. To test the involvement of Tau in stress-induced impairments of cognition, we investigated the impact of stress on cognitive behavior, neuronal structure, and the synaptic proteome in the prefrontal cortex (PFC) of Tau knock-out (Tau-KO) and wild-type (WT) mice. Whereas exposure to chronic stress resulted in atrophy of apical dendrites and spine loss in PFC neurons as well as significant impairments in working memory in WT mice, such changes were absent in Tau-KO animals. Quantitative proteomic analysis of PFC synaptosomal fractions, combined with transmission electron microscopy analysis, suggested a prominent role for mitochondria in the regulation of the effects of stress. Specifically, chronically stressed animals exhibit Tau-dependent alterations in the levels of proteins involved in mitochondrial transport and oxidative phosphorylation as well as in the synaptic localization of mitochondria in PFC. These findings provide evidence for a causal role of Tau in mediating stress-elicited neuronal atrophy and cognitive impairment and indicate that Tau may exert its effects through synaptic mitochondria.
SummaryDementia is the cardinal feature of Alzheimer's disease (AD), yet the clinical symptoms of this disorder also include a marked loss of motor function. Tau abnormal hyperphosphorylation and malfunction are well‐established key events in AD neuropathology but the impact of the loss of normal Tau function in neuronal degeneration and subsequent behavioral deficits is still debated. While Tau reduction has been increasingly suggested as therapeutic strategy against neurodegeneration, particularly in AD, there is controversial evidence about whether loss of Tau progressively impacts on motor function arguing about damage of CNS motor components. Using a variety of motor‐related tests, we herein provide evidence of an age‐dependent motor impairment in Tau−/− animals that is accompanied by ultrastructural and functional impairments of the efferent fibers that convey motor‐related information. Specifically, we show that the sciatic nerve of old (17–22‐months) Tau−/− mice displays increased degenerating myelinated fibers and diminished conduction properties, as compared to age‐matched wild‐type (Tau+/+) littermates and younger (4–6 months) Tau−/− and Tau+/+ mice. In addition, the sciatic nerves of Tau−/− mice exhibit a progressive hypomyelination (assessed by g‐ratio) specifically affecting large‐diameter, motor‐related axons in old animals. These findings suggest that loss of Tau protein may progressively impact on peripheral motor system.
BackgroundAttrition or losses from the health workforce exacerbate critical shortages of health workers and can be a barrier to countries reaching their universal health coverage and equity goals. Despite the importance of accurate estimates of the attrition rate (and in particular the voluntary attrition rate) to conduct effective workforce planning, there is a dearth of an agreed definition, information and studies on this topic.MethodsWe conducted a rapid review of studies published since 2005 on attrition rates of health workers from the workforce in different regions and settings; 1782 studies were identified, of which 51 were included in the study. In addition, we analysed data from the State of the World’s Midwifery (SoWMy) 2014 survey and associated regional survey for the Arab states on the annual voluntary attrition rate for sexual, reproductive, maternal and newborn health workers (mainly midwives, doctors and nurses) in the 79 participating countries.ResultsThere is a diversity of definitions of attrition and barely any studies distinguish between total and voluntary attrition (i.e. choosing to leave the workforce). Attrition rate estimates were provided for different periods of time, ranging from 3 months to 12 years, using different calculations and data collection systems. Overall, the total annual attrition rate varied between 3 and 44% while the voluntary annual attrition rate varied between 0.3 to 28%. In the SoWMy analysis, 49 countries provided some data on voluntary attrition rates of their SRMNH cadres. The average annual voluntary attrition rate was 6.8% across all cadres.ConclusionAttrition, and particularly voluntary attrition, is under-recorded and understudied. The lack of internationally comparable definitions and guidelines for measuring attrition from the health workforce makes it very difficult for countries to identify the main causes of attrition and to develop and test strategies for reducing it. Standardized definitions and methods of measuring attrition are required.Electronic supplementary materialThe online version of this article (doi:10.1186/s12960-017-0195-2) contains supplementary material, which is available to authorized users.
A B S T R A C TForced imbibition was performed in reservoir sandstone by injecting water into a dry sample. The injection was monitored with X-ray computed tomography and acoustic acquisition to simultaneously visualize the displacement of the fluid and quantify its presence by calculating saturation and P-wave velocities.We observed a strong influence when changing the injection rates on the acoustic response. Upon decreasing the injection rate from 5 mL/h to 0.1 mL/h, P-wave velocities decreased sharply: 100 m/s in 1 h. This behaviour is related to the partially saturated conditions of the sample (76% of saturation) before decreasing the injection rate. The air that is still trapped is free to move due to a decrease of pore pressure that is no longer forced by the higher injection rate. After 1 hour, P-wave velocities started increasing with small changes in saturation. Stopping injection for 16 hrs decreased saturation by 8% and P-wave velocities by 100 m/s. Restarting injection at 5 mL/h increased saturation to 76% while P-wave velocities fluctuated considerably for 2 hrs until they stabilized at 2253 m/s. Through the computed tomography scans we observed a water front advancing through the sample and how its shape changed from a plane to a curve after decreasing the injection rate.
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