The Challenges of Developing an Instrument to Assess Health Provider Motivation at Primary Care Level in Rural Burkina Faso, Ghana and Tanzania.

The quality of health care depends on the competence and motivation of the health workers that provide it. In the West, several tools exist to measure worker motivation, and some have been applied to the health sector. However, none have been validated for use in sub-Saharan Africa. The complexity of such tools has also led to concerns about their application at primary care level. To develop a common instrument to monitor any changes in maternal and neonatal health (MNH) care provider motivation resulting from the introduction of pilot interventions in rural, primary level facilities in Ghana, Burkina Faso, and Tanzania. Initially, a conceptual framework was developed. Based upon this, a literature review and preliminary qualitative research, an English-language instrument was developed and validated in an iterative process with experts from the three countries involved. The instrument was then piloted in Ghana. Reliability testing and exploratory factor analysis were used to produce a final, parsimonious version. This paper describes the actual process of developing the instrument. Consequently, the concepts and items that did not perform well psychometrically at pre-test are first presented and discussed. The final version of the instrument, which comprises 42 items for self-assessment and eight for peer-assessment, is then shown. This is followed by a presentation and discussion of the findings from first use of the instrument with MNH providers from 12 rural, primary level facilities in each of the three countries. It is possible to undertake work of this nature at primary health care level, particularly if the instruments are kept as straightforward as possible and well introduced. However, their development requires very lengthy preparatory periods. The effort needed to adapt such instruments for use in different countries within the region of sub-Saharan Africa should not be underestimated

PPARgamma activation attenuates T-lymphocyte-dependent inflammation of adipose tissue and development of insulin resistance in obese mice

<p>Abstract</p> <p>Background</p> <p>Inflammation of adipose tissue (AT) has been recently accepted as a first step towards obesity-mediated insulin resistance. We could previously show that mice fed with high fat diet (HFD) develop systemic insulin resistance (IR) and glucose intolerance (GI) associated with CD4-positive T-lymphocyte infiltration into visceral AT. These T-lymphocytes, when enriched in AT, participate in the development of fat tissue inflammation and subsequent recruitment of proinflammatory macrophages. The aim of this work was to elucidate the action of the insulin sensitizing PPARgamma on T-lymphocyte infiltration during development of IR, and comparison of the PPARgamma-mediated anti-inflammatory effects of rosiglitazone and telmisartan in diet-induced obesity model (DIO-model) in mice.</p> <p>Methods</p> <p>In order to investigate the molecular mechanisms underlying early development of systemic insulin resistance and glucose intolerance male C57BL/6J mice were fed with high fat diet (HFD) for 10-weeks in parallel to the pharmacological intervention with rosiglitazone, telmisartan, or vehicle.</p> <p>Results</p> <p>Both rosiglitazone and telmisartan were able to reduce T-lymphocyte infiltration into AT analyzed by quantitative analysis of the T-cell marker CD3gamma and the chemokine SDF1alpha. Subsequently, both PPARgamma agonists were able to attenuate macrophage infiltration into AT, measured by the reduction of MCP1 and F4/80 expression. In parallel to the reduction of AT-inflammation, ligand-activated PPARgamma improved diet-induced IR and GI.</p> <p>Conclusion</p> <p>Together the present study demonstrates a close connection between PPARgamma-mediated anti-inflammation in AT and systemic improvement of glucose metabolism identifying T-lymphocytes as one cellular mediator of PPARgamma´s action.</p

Effect of everolimus-based drug regimens on CMV-specific T-cell functionality after renal transplantation: 12-month ATHENA subcohort-study results

Post-transplant cytomegalovirus (CMV) infections and increased viral replication are associated with CMV-specific T-cell anergy. In the ATHENA-study, de-novo everolimus (EVR) with reduced-exposure tacrolimus (TAC) or cyclosporine (CyA) showed significant benefit in preventing CMV infections in renal transplant recipients as compared to standard TAC + mycophenolic acid (MPA). However, immunomodulatory mechanisms for this effect remain largely unknown. Ninety patients from the ATHENA-study completing the 12-month visit on-treatment (EVR + TAC n = 28; EVR + CyA n = 19; MPA + TAC n = 43) were included in a posthoc analysis. Total lymphocyte subpopulations were quantified. CMV-specific CD4 T cells were determined after stimulation with CMV-antigen, and cytokine-profiles and various T-cell anergy markers were analyzed using flow cytometry. While 25.6% of MPA + TAC-treated patients had CMV-infections, no such events were reported in EVR-treated patients. Absolute numbers of lymphocyte subpopulations were comparable between arms, whereas the percentage of regulatory T cells was significantly higher with EVR + CyA versus MPA + TAC (p = 0.019). Despite similar percentages of CMV-specific T cells, their median expression of CTLA-4 and PD-1 was lower with EVR + TAC (p < 0.05 for both) or EVR + CyA (p = 0.045 for CTLA-4) compared with MPA + TAC. Moreover, mean percentages of multifunctional CMV-specific T cells were higher with EVR + TAC (27.2%) and EVR + CyA (29.4%) than with MPA + TAC (19.0%). In conclusion, EVR-treated patients retained CMV-specific T-cell functionality, which may contribute to enhanced protection against CMV infections

Guideline for the management of myasthenic syndromes

Myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), and congenital myasthenic syndromes (CMS) represent an etiologically heterogeneous group of (very) rare chronic diseases. MG and LEMS have an autoimmune-mediated etiology, while CMS are genetic disorders. A (strain dependent) muscle weakness due to neuromuscular transmission disorder is a common feature. Generalized MG requires increasingly differentiated therapeutic strategies that consider the enormous therapeutic developments of recent years. To include the newest therapy recommendations, a comprehensive update of the available German-language guideline ‘Diagnostics and therapy of myasthenic syndromes’ has been published by the German Neurological society with the aid of an interdisciplinary expert panel. This paper is an adapted translation of the updated and partly newly developed treatment guideline. It defines the rapid achievement of complete disease control in myasthenic patients as a central treatment goal. The use of standard therapies, as well as modern immunotherapeutics, is subject to a staged regimen that takes into account autoantibody status and disease activity. With the advent of modern, fast-acting immunomodulators, disease activity assessment has become pivotal and requires evaluation of the clinical course, including severity and required therapies. Applying MG-specific scores and classifications such as Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Foundation of America allows differentiation between mild/moderate and (highly) active (including refractory) disease. Therapy decisions must consider age, thymic pathology, antibody status, and disease activity. Glucocorticosteroids and the classical immunosuppressants (primarily azathioprine) are the basic immunotherapeutics to treat mild/moderate to (highly) active generalized MG/young MG and ocular MG. Thymectomy is indicated as a treatment for thymoma-associated MG and generalized MG with acetylcholine receptor antibody (AChR-Ab)-positive status. In (highly) active generalized MG, complement inhibitors (currently eculizumab and ravulizumab) or neonatal Fc receptor modulators (currently efgartigimod) are recommended for AChR-Ab-positive status and rituximab for muscle-specific receptor tyrosine kinase (MuSK)-Ab-positive status. Specific treatment for myasthenic crises requires plasmapheresis, immunoadsorption, or IVIG. Specific aspects of ocular, juvenile, and congenital myasthenia are highlighted. The guideline will be further developed based on new study results for other immunomodulators and biomarkers that aid the accurate measurement of disease activity

The PI3K and MAPK/p38 pathways control stress granule assembly in a hierarchical manner

All cells and organisms exhibit stress-coping mechanisms to ensure survival. Cytoplasmic protein-RNA assemblies termed stress granules are increasingly recognized to promote cellular survival under stress. Thus, they might represent tumor vulnerabilities that are currently poorly explored. The translation-inhibitory eIF2α kinases are established as main drivers of stress granule assembly. Using a systems approach, we identify the translation enhancers PI3K and MAPK/p38 as pro-stress-granule-kinases. They act through the metabolic master regulator mammalian target of rapamycin complex 1 (mTORC1) to promote stress granule assembly. When highly active, PI3K is the main driver of stress granules; however, the impact of p38 becomes apparent as PI3K activity declines. PI3K and p38 thus act in a hierarchical manner to drive mTORC1 activity and stress granule assembly. Of note, this signaling hierarchy is also present in human breast cancer tissue. Importantly, only the recognition of the PI3K-p38 hierarchy under stress enabled the discovery of p38’s role in stress granule formation. In summary, we assign a new pro-survival function to the key oncogenic kinases PI3K and p38, as they hierarchically promote stress granule formation

Changes in magnetic resonance mammography due to hormone replacement therapy

BACKGROUND: The aim of the present article is to investigate effects of hormone replacement therapy (HRT) on contrast medium enhancement patterns in postmenopausal patients during magnetic resonance mammography (MRM). MATERIALS AND METHODS: Two hundred and fifteen patients receiving hormonal medication were divided into four groups: 150 patients with 1 MRM during HRT (group A), 13 patients with 2 MRMs under HRT (group B), 30 patients with 1 MRM during HRT and 1 MRM after HRT withdrawal (group C), and 22 women with 1 MRM after HRT withdrawal (group D). Dynamic MRM was performed at 1.5 Tesla. Signal intensity changes were characterized by five time curves: minimal enhancement (type I), weak continuous enhancement (type II), strong continuous enhancement (type III), and a steep initial slope followed by a plateau phenomenon (type IV) or a washout effect (type V). RESULTS: Of all 193 patients under HRT (group A + group B + group C), 60 patients (31.1%) showed curve type I, 88 patients (45.6%) showed type II and 45 patients (23.3%) showed type III. There were significant differences to 52 patients after HRT withdrawal (group C + group D) (P < 0.0001), with 42 patients (80.8%) for curve type I, 8 patients (15.4%) for type II, and 2 patients (3.8%) for type III. In both MRM sessions in group B, 69% of the patients showed identical curve types without significant differences (P = 0.375). In group C, 28 of 30 patients (93%) dropped to lower curve types with significant differences in curve types during and after HRT (P < 0.0001). CONCLUSION: The majority of patients receiving postmenopausal HRT showed bilateral symmetrical, continuous enhancement without evidence of a plateau phenomenon or a washout effect due to HRT in MRM. Hormonal effects could be proven and were reproducible and reversible

Rehydration Data for the Materials International Space Station Experiment (MISSE) Polymer Films

Atomic oxygen erosion of polymers in low Earth orbit (LEO) poses a serious threat to spacecraft performance and durability. Forty thin film polymer and pyrolytic graphite samples, collectively called the PEACE (Polymer Erosion and Contamination Experiment) Polymers, were exposed to the LEO space environment on the exterior of the ISS for nearly four years as part of the Materials International Space Station Experiment 1 & 2 (MISSE 1 & 2) mission. The purpose of the MISSE 2 PEACE Polymers experiment was to determine the atomic oxygen (AO) erosion yield (E(sub y), volume loss per incident oxygen atom) of a wide variety of polymers exposed to the LEO space environment. The Ey values were determined based on mass loss measurements. Because many polymeric materials are hygroscopic, the pre-flight and post-flight mass measurements were obtained using dehydrated samples. To maximize the accuracy of the mass measurements, obtaining dehydration data for each of the polymers was desired to ensure that the samples were fully dehydrated before weighing. A comparison of dehydration and rehydration data showed that rehydration data mirrors dehydration data, and is easier and more reliable to obtain. Tests were also conducted to see if multiple samples could be dehydrated and weighed sequentially. Rehydration curves of 43 polymers and pyrolytic graphite were obtained. This information was used to determine the best pre-flight, and post-flight, mass measurement procedures for the MISSE 2 PEACE Polymers experiment, and for subsequent NASA Glenn Research Center MISSE polymer flight experiments

Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects

Mental disorders are highly comorbid and occur together with physical diseases, which are often considered to arise from separate pathogenic pathways. We observed in alcohol-dependent patients increased serum activity of neutral sphingomyelinase. A genetic association analysis in 456,693 volunteers found associations of haplotypes of SMPD3 coding for NSM-2 (NSM) with alcohol consumption, but also with affective state, and bone mineralisation. Functional analysis in mice showed that NSM controls alcohol consumption, affective behaviour, and their interaction by regulating hippocampal volume, cortical connectivity, and monoaminergic responses. Furthermore, NSM controlled bone–brain communication by enhancing osteocalcin signalling, which can independently supress alcohol consumption and reduce depressive behaviour. Altogether, we identified a single gene source for multiple pathways originating in the brain and bone, which interlink disorders of a mental–physical co-morbidity trias of alcohol abuse—depression/anxiety—bone disorder. Targeting NSM and osteocalcin signalling may, thus, provide a new systems approach in the treatment of a mental–physical co-morbidity trias

Bourdieusian Reflections on Language: Unavoidable Conditions of the Real Speech Situation

The main purpose of this paper is to shed light on Pierre Bourdieu’s conception of language. Although he has dedicated a significant part of his work to the study of language and even though his analysis of language has been extensively discussed in the literature, almost no attention has been paid to the factthat Bourdieu’s account of language is based on a number of ontological presuppositions, that is, on a set of universal assumptions about the very nature of language. This article aims to fill this gap in the literature by offering a detailed overview of 10 key features which, from a Bourdieusian point of view, can be regarded as inherent in language. On the basis of this enquiry,the study seeks todemonstrate that——contraryto commonbelief——there is not only a Bourdieusian sociology of language but also a Bourdieusian philosophy of language, which provides a useful theoretical framework for examining the unavoidable conditions of the real speech situation. The paper draws to a close by reflecting on the flaws and limitations of Bourdieu’s approach to language