Sphingolipid metabolites in neural signalling and function

Sphingolipid metabolites, such as ceramide, sphingosine, sphingosine-1-phosphate (S1P) and complex sphingolipids (gangliosides), are recognized as molecules capable of regulating a variety of cellular processes. The role of sphingolipid metabolites has been studied mainly in non-neuronal tissues. These studies have underscored their importance as signals transducers, involved in control of proliferation, survival, differentiation and apoptosis. In this review, we will focus on studies performed over the last years in the nervous system, discussing the recent developments and the current perspectives in sphingolipid metabolism and functions.     

Liver transplant and hepatitis C in methadone maintenance therapy: a case report

Methadone maintenance therapy for the treatment of opioid dependence continues to carry a social stigma. Until recently, patients on methadone were not considered for liver transplantation. We describe the first case of a patient on methadone who received a liver transplant for end stage liver disease and was successfully treated for recurrent hepatitis C. More than five years post transplant and three years post viral clearance, the patient continues to do well and is stable on low-dose methadone. This case emphasizes the need to reconsider the non-evidence based policy adopted by transplant centers that require methadone maintenance therapy patients to stop methadone prior to consideration for transplant evaluation.     

Macrophages and translymphatic absorption represent the first line of host defense of the peritoneal cavity

To quantitate the host defenses of the rat peritoneal cavity, nonviable radiolabeled Escherichia coli were injected intraperitoneally and clearance, leukocyte influx, and phagocytosis were examined. Macrophages (MCs) were present initially and remained relatively constant in number. The polymorphonuclear leukocyte (PMN) response began at one to two hours and was maximal at 24 to 72 hours. A previously unidentified inoculum-dependent PMN response was defined. Clearance and phagocytosis were extremely rapid, and few (less than 3%) free bacteria were present after two hours. Phagocytic activity of MCs and PMNs was identical, but MCs were numerically predominant initially and thus accounted for the majority of early phagocytosis. Thus, MC phagocytosis and clearance represent the primary line of host peritoneal defenses. We hypothesize that the subsequent inoculum-dependent PMN response may have evolved to cope with those larger inocula for which this initial response is inadequate.     

Public health laws and implications for a national accreditation program: parallel roadways without intersection?

Public health law has been one of the leading contributors to the extension of life expectancy in the 20th century. Nonetheless, the legal infrastructure supporting public health law in the United States is underdeveloped and nonuniform. With national interest growing in public health agency accreditation, the individual legal approach taken by states may pose an obstacle to wholesale adoption of a proposed voluntary national model. This article describes the legal foundations supporting accreditation or assessment programs in states participating in the Multi-State Learning Collaborative, a project funded by the Robert Wood Johnson Foundation. The Turning Point Model State Public Health Act is recommended as one option to resolve the current impasse, assist in acceptance of a national accreditation model, and provide a common public health legal infrastructure.     

‘Translation is not enough’: using the Global Person Generated Index (GPGI) to assess individual quality of life in Bangladesh,Thailand, and Ethiopia

Currently few subjective measures of Quality of Life (QoL) are available for use in developing countries, which limits their theoretical, methodological, and practical contribution (for example, exploring the relationship between economic development and QoL, and ensuring effective and equitable service provision). One reason for this is the difficulty of ensuring that translated measures preserve conceptual, item, semantic, operational, measurement; and functional equivalence (Herdman, M., Fox-Rushby, J., & Badia, X. (1998). Quality of Life Research, 7, 331), which is illustrated by an account of the translation, pre-piloting, and administration of a new individualised QoL measure, the Global Person Generated Index or 'GPGI'. The GPGI is based on the widely used Patient Generated Index (Ruta, Camfield, & Martin, (2004) Quality of Life Research, 13, 1545.) and offers many of the advantages of the participatory approaches commonly used in developing countries, with added methodological rigour, and quantitative outcomes. It was successfully validated in Bangladesh, Thailand, and Ethiopia, using quantitative and qualitative methods--open-ended, semi-structured interviews (SSIs), conducted immediately post-administration. Both the measure and method of 'qualitative validation' described later in the paper offer an exciting alternative for future researchers and practitioners in this field. The quantitative results suggest the GPGI shows cultural sensitivity, and is able to capture both the areas that are important to respondents, and aspects of life one would expect to impact on QoL in developing countries. There were strong correlation between scores from the GPGI and SSIs for the area of health, and moderate correlations for 'material wellbeing' (MWB)('Material wellbeing' refers to respondents' perceptions of their achievement in the areas of farming, debt reduction, assets, crops, livestock, job, land, property, and agriculture) and children. Weak to moderate correlations were observed between the Satisfaction with Life Scale and the GPGI; however, the highest coefficient was between the GPGI and the most conceptually similar item. Statistically significant differences were seen in GPGI scores between rich and poor, urban and rural respondents, and different countries. Health and material wellbeing scores, derived from the SSIs, also showed a linear relationship with GPGI scores, with a suggestion of curvilinearity at the higher levels, as predicted by a general QoL causal model. In conclusion, the GPGI has great potential for use in this area, especially when supported by extensive interviewer training, and supplemented with a cognitive appraisal schedule.     

Characterization of the Medical Symptom Validity Test in evaluation of clinically referred memory disorders clinic patients.

We prospectively evaluated performance of 63 referrals to a memory disorders clinic who received the Medical Symptom Validity Test (MSVT) as part of their standard neuropsychological evaluation. The patients were grouped based on independent medical diagnoses and presence or absence of a potential financial incentive to under-perform. Twenty-seven patients (42.9%) scored below cutoffs on the MSVT symptom validity indices. Two individuals in the potential financial incentive group showed clear signs of invalid responding (18.2%). Twenty-two of the remaining 25 patients who failed the symptom validity indices corresponded to the dementia profile. Three individuals did not correspond to the dementia profile but are thought to have performed validly representing a 4.8% false positive rate. When considering all MSVT indices, the base rate of invalid responding in the potential financial incentive to under-perform group increased to 27.3%. Combining all groups our base rate of invalid responding was 4.8%. Specific performances are presented.     

Neuropsychological assessment, neuroimaging, and neuropsychiatric evaluation in pediatric and adult patients with sickle cell disease (SCD)

Traditionally, neuropsychological deficits due to Sickle Cell Disease (SCD) have been understudied in adults. We have begun to suspect, however, that symptomatic and asymptomatic Cerebrovascular Events (CVE) may account for an alarming number of deficits in this population. In the current brief review, we critically evaluated the pediatric and adult literatures on the neurocognitive effects of SCD. We highlighted the studies that have been published on this topic and posit that early detection of CVE via neurocognitive testing, neuropsychiatric evaluations, and neuroimaging may significantly reduce adult cognitive and functional morbidities.     

Public health capacity building in southeastern Europe: a partnership between the Open Society Institute and the US Centers for Disease Control and Prevention.

The political disintegration of former Yugoslavia inaugurated in 1991 resulted in the decentralization of health systems in the federation's successor nation-states. Efforts by the Open Society Institute improved public health planning and management needs consequent to health sector changes. Beginning in Croatia in 2001, the Institute developed ongoing collaborations between Andrija Stampar School of Public Health and the US Centers for Disease Control and Prevention. In 2003 and 2004, it expanded its project to include the republics of Macedonia and of Serbia and Montenegro.