Delayed priming promotes CNS regeneration post-rhizotomy in Neurocan and Brevican-deficient mice

A wealth of literature has provided evidence that reactive tissue at the site of CNS injury is rich in chondroitin sulfate proteoglycans which may contribute to the non-permissive nature of the CNS. We have recently demonstrated using a murine model of human brachial plexus injury that the chondroitin sulfate proteoglycans Neurocan and Brevican are differentially expressed by two subsets of astrocytes in the spinal cord dorsal root entry zone (DREZ) following dorsal root lesion (Beggah et al., Neuroscience 133: 749-762, 2005). However, direct evidence for a growth-inhibitory role of these proteoglycans in vivo is still lacking. We therefore performed dorsal root lesion (rhizotomy) in mice deficient in both Neurocan and Brevican. Rhizotomy in these animals resulted in no significant increase in the number of sensory fibres regenerating through the DREZ compared to genetically matched controls. Likewise, a conditioning peripheral nerve lesion prior to rhizotomy, which increases the intrinsic growth capacity of sensory neurons, enhanced growth to the same extent in transgenic and control mice, indicating that absence of these proteoglycans alone is not sufficient to further promote entry into the spinal cord. In contrast, when priming of the median nerve was performed at a clinically relevant time, i.e. 7 weeks post-rhizotomy, the growth of a subpopulation of sensory axons across the DREZ was facilitated in Neurocan/Brevican-deficient, but not in control animals. This demonstrates for the first time that (i) Neurocan and/or Brevican contribute to the non-permissive environment of the DREZ several weeks after lesion and that (ii) delayed stimulation of the growth program of sensory neurons can facilitate regeneration across the DREZ provided its growth-inhibitory properties are attenuated. Post-injury enhancement of the intrinsic growth capacity of sensory neurons combined with removal of inhibitory chondroitin sulfate proteoglycans may therefore help to restore sensory function and thus attenuate the chronic pain resulting from human brachial plexus injur

GDNF reduces drug-induced rotational behavior after medial forebrain bundle transection by a mechanism not involving striatal dopamine

Parkinson's disease (PD) is characterized by the progressive loss of the substantia nigra (SN) dopaminergic neurons projecting to the striatum. Neurotrophic factors may have the potential to prevent or slow down the degenerative process occurring in PD. To that end, we examined whether low amounts of glial cell line-derived neurotrophic factor (GDNF) continuously released from polymer-encapsulated genetically engineered cells are able to prevent the loss of tyrosine hydroxylase immunoreactivity (TH-IR) in SN neurons and ameliorate the amphetamine-induced rotational asymmetry in rats that have been subjected to a unilateral medial forebrain bundle (MFB) axotomy. Baby hamster kidney (BHK) cells transfected with the cDNA for GDNF were encapsulated in a polymer fiber and implanted unilaterally at a location lateral to the MFB and rostral to the SN. ELISA assays before implantation show that the capsules release approximately 5 ng of GDNF/capsule per day. One week later, the MFB was axotomized unilaterally ipsilateral to the capsule placement. Seven days later, the animals were tested for amphetamine-induced rotational asymmetry and killed. The striatum was excised and analyzed either for catecholamine content or TH-IR, while the SN was immunostained for the presence of TH-IR. GDNF did not prevent the loss of dopamine in the striatum. However, GDNF significantly rescued TH-IR neurons in the SN pars compacta. Furthermore, GDNF also significantly reduced the number of turns per minute ipsilateral to the lesion under the influence of amphetamine. Improvement of rotational behavior in the absence of dopaminergic striatal reinnervation may reflect neuronal plasticity in the SN, as suggested by the dendritic sprouting observed in animals receiving GDNF. These results illustrate that the continuous release of low levels of GDNF close to the SN is capable of protecting the nigral dopaminergic neurons from an axotomy-induced lesion and significantly improving pharmacological rotational behavior by a mechanism other than dopaminergic striatal reinnervation

Tidal triggering of earthquakes in the Swabian Jura?

Several statistical tests were used to investigate the possibility that the earthquakes in the Swabian Jura are triggered by the tidal stress in the Earth. The results provide weak evidence that the earthquakes tend to occur when the tidal shear stress on the fault plane in the direction supporting the tectonic stress is greatest. A comparison of some of the statistical methods available for investigating tidal triggering effects is made.         ARK: https://n2t.net/ark:/88439/y090017 Permalink: https://geophysicsjournal.com/article/41 &nbsp

Monitoring and evaluation of human resources for health: an international perspective

BACKGROUND: Despite the undoubted importance of human resources to the functions of health systems, there is little consistency between countries in how human resource strategies are monitored and evaluated. This paper presents an integrated approach for developing an evidence base on human resources for health (HRH) to support decision-making, drawing on a framework for health systems performance assessment. METHODS: Conceptual and methodological issues for selecting indicators for HRH monitoring and evaluation are discussed, and a range of primary and secondary data sources that might be used to generate indicators are reviewed. Descriptive analyses are conducted drawing primarily on one type of source, namely routinely reported data on the numbers of health personnel and medical schools as covered by national reporting systems and compiled by the World Health Organization. Regression techniques are used to triangulate a given HRH indicator calculated from different data sources across multiple countries. RESULTS: Major variations in the supply of health personnel and training opportunities are found to occur by region. However, certain discrepancies are also observed in measuring the same indicator from different sources, possibly related to the occupational classification or to the sources' representation. CONCLUSION: Evidence-based information is needed to better understand trends in HRH. Although a range of sources exist that can potentially be used for HRH assessment, the information that can be derived from many of these individual sources precludes refined analysis. A variety of data sources and analytical approaches, each with its own strengths and limitations, is required to reflect the complexity of HRH issues. In order to enhance cross-national comparability, data collection efforts should be processed through the use of internationally standardized classifications (in particular, for occupation, industry and education) at the greatest level of detail possible

Automated Assessment of Pavlovian Conditioned Freezing and Shock Reactivity in Mice Using the Video Freeze System

The Pavlovian conditioned freezing paradigm has become a prominent mouse and rat model of learning and memory, as well as of pathological fear. Due to its efficiency, reproducibility and well-defined neurobiology, the paradigm has become widely adopted in large-scale genetic and pharmacological screens. However, one major shortcoming of the use of freezing behavior has been that it has required the use of tedious hand scoring, or a variety of proprietary automated methods that are often poorly validated or difficult to obtain and implement. Here we report an extensive validation of the Video Freeze system in mice, a “turn-key” all-inclusive system for fear conditioning in small animals. Using digital video and near-infrared lighting, the system achieved outstanding performance in scoring both freezing and movement. Given the large-scale adoption of the conditioned freezing paradigm, we encourage similar validation of other automated systems for scoring freezing, or other behaviors

Expanding the Taxonomy of (Mis-)Recognition in the Economic Sphere

This paper makes a contribution to debates in recognition theory by expanding the taxonomy of (mis-)recognition in the economic sphere. We argue that doing justice to the variety of ways in which recognition is engaged in economic relationships requires: (1) to take into consideration not just the recognition principle of esteem, but also (various aspects of) need and respect; (2) to distinguish a productive from a consumptive dimension with regards to each principle of recognition (need, esteem and respect); (3) and to identify the specific economic relationship at stake (e.g. between consumers and producers, or between employers and employees). In this way, we can account for the diversity of demands for recognition made in the economic sphere, explain what underpins them, and bring structure into these diverse phenomena. What is more, our expanded taxonomy is a useful tool for social pathology theorists. They have to appreciate the full range of variants of misrecognition when diagnosing pathologies of misrecognition in the economic sphere

Too few staff, too many patients: A qualitative study of the impact on obstetric care providers and on quality of care in Malawi

Background: Shortages of staff have a significant and negative impact on maternal outcomes in low-income countries, but the impact on obstetric care providers in these contexts is less well documented. Despite the government of Malawi's efforts to increase the number of human resources for health, maternal mortality rates remain persistently high. Health workers' perceptions of insufficient staff or time to carry out their work can predict key variables concerning motivation and attrition, while the resulting sub-standard care and poor attitudes towards women dissuade women from facility-based delivery. Understanding the situation from the health worker perspective can inform policy options that may contribute to a better working environment for staff and improved quality of care for Malawi's women. Methods: A qualitative research design, using critical incident interviews, was used to generate a deep and textured understanding of participants' experiences. Eligible participants had performed at least one of the emergency obstetric care signal functions a in the previous three months and had experienced a demotivating critical incident within the same timeframe. Data were analysed using NVivo software. Results: Eighty-four interviews were conducted. Concerns about staff shortages and workload were key factors for over 40% of staff who stated their intention to leave their current post and for nearly two-thirds of the remaining health workers who were interviewed. The main themes emerging were: too few staff, too many patients; lack of clinical officers/doctors; inadequate obstetric skills; undermining performance and professionalism; and physical and psychological consequences for staff. Underlying factors were inflexible scheduling and staff allocations that made it impossible to deliver quality care. Conclusion: This study revealed the difficult circumstances under which maternity staff are operating and the professional and emotional toll this exacts. Systems failures and inadequate human resource management are key contributors to the gaps in provision of obstetric care and need to be addressed. Thoughtful strategies that match supply to demand, coupled with targeted efforts to support health workers, are necessary to mitigate the effects of working in this context and to improve the quality of obstetric care for women in Malawi

Remarks on the Concept of Critique in Habermasian Thought

The main purpose of this paper is to examine the concept of critique in Habermasian thought. Given that the concept of critique is a central theoretical category in the work of the Frankfurt School, it comes as a surprise that little in the way of a systematic account which sheds light on the multifaceted meanings of the concept of critique in Habermas’s oeuvre can be found in the literature. This paper aims to fill this gap by exploring the various meanings that Habermas attributes to the concept of critique in 10 key thematic areas of his writings: (1) the public sphere, (2) knowledge, (3) language, (4) morality, (5) ethics, (6) evolution, (7) legitimation, (8) democracy, (9) religion, and (10) modernity. On the basis of a detailed analysis of Habermas’s multifaceted concerns with the nature and function of critique, the study seeks to demonstrate that the concept of critique can be considered not only as a constitutive element but also as a normative cornerstone of Habermasian thought. The paper draws to a close by reflecting on some of the limitations of Habermas’s conception of critique, arguing that in order to be truly critical in the Habermasian sense we need to turn the subject of critique into an object of critique

Uses of population census data for monitoring geographical imbalance in the health workforce: snapshots from three developing countries

BACKGROUND: Imbalance in the distribution of human resources for health (HRH), eventually leading to inequities in health services delivery and population health outcomes, is an issue of social and political concern in many countries. However, the empirical evidence to support decision-making is often fragmented, and many standard data sources that can potentially produce statistics relevant to the issue remain underused, especially in developing countries. This study investigated the uses of demographic census data for monitoring geographical imbalance in the health workforce for three developing countries, as a basis for formulation of evidence-based health policy options. METHODS: Population-based indicators of geographical variations among HRH were extracted from census microdata samples for Kenya, Mexico and Viet Nam. Health workforce statistics were matched against international standards of occupational classification to control for cross-national comparability. Summary measures of inequality were calculated to monitor the distribution of health workers across spatial units and by occupational group. RESULTS: Strong inequalities were found in the geographical distribution of the health workforce in all three countries, with the highest densities of HRH tending to be found in the capital areas. Cross-national differences were found in the magnitude of distributional inequality according to occupational group, with health professionals most susceptible to inequitable distribution in Kenya and Viet Nam but less so in Mexico compared to their associate professional counterparts. Some discrepancies were suggested between mappings of occupational information from the raw data with the international system, especially for nursing and midwifery specializations. CONCLUSIONS: The problem of geographical imbalance among HRH across countries in the developing world holds important implications at the local, national and international levels, in terms of constraints for the effective deployment, management and retention of HRH, and ultimately for the equitable delivery of health services. A number of advantages were revealed of using census data in health research, notably the potential for producing detailed statistics on health workforce characteristics at the sub-national level. However, lack of consistency in the compilation and processing of occupational information over time and across countries continues to hamper comparative analyses for HRH policy monitoring and evaluation