Gray-matter volume, midbrain dopamine D2/D3 receptors and drug craving in methamphetamine users.

Dysfunction of the mesocorticolimbic system has a critical role in clinical features of addiction. Despite evidence suggesting that midbrain dopamine receptors influence amphetamine-induced dopamine release and that dopamine is involved in methamphetamine-induced neurotoxicity, associations between dopamine receptors and gray-matter volume have been unexplored in methamphetamine users. Here we used magnetic resonance imaging and [(18)F]fallypride positron emission tomography, respectively, to measure gray-matter volume (in 58 methamphetamine users) and dopamine D2/D3 receptor availability (binding potential relative to nondisplaceable uptake of the radiotracer, BPnd) (in 31 methamphetamine users and 37 control participants). Relationships between these measures and self-reported drug craving were examined. Although no difference in midbrain D2/D3 BPnd was detected between methamphetamine and control groups, midbrain D2/D3 BPnd was positively correlated with gray-matter volume in the striatum, prefrontal cortex, insula, hippocampus and temporal cortex in methamphetamine users, but not in control participants (group-by-midbrain D2/D3 BPnd interaction, P<0.05 corrected for multiple comparisons). Craving for methamphetamine was negatively associated with gray-matter volume in the insula, prefrontal cortex, amygdala, temporal cortex, occipital cortex, cerebellum and thalamus (P<0.05 corrected for multiple comparisons). A relationship between midbrain D2/D3 BPnd and methamphetamine craving was not detected. Lower midbrain D2/D3 BPnd may increase vulnerability to deficits in gray-matter volume in mesocorticolimbic circuitry in methamphetamine users, possibly reflecting greater dopamine-induced toxicity. Identifying factors that influence prefrontal and limbic volume, such as midbrain BPnd, may be important for understanding the basis of drug craving, a key factor in the maintenance of substance-use disorders

eXCloud: Transparent runtime support for scaling mobile applications in cloud

Cloud computing augments applications with ease-of-access to the enormous resources on the Internet. Combined with mobile computing technologies, mobile applications can exploit the Cloud everywhere by statically distributing code segments or dynamically migrating running processes onto cloud services. Existing migration techniques are however too coarse-grained for mobile devices, so the overheads often offset the benefits of migration. To build a truly elastic mobile cloud computing infrastructure, we introduce eXCloud (eXtensible Cloud) - a middleware system with multi-level mobility support, ranging from as coarse as a VM instance to as fine as a runtime stack frame, and allows resources to be integrated and used dynamically. In eXCloud, a stack-on-demand (SOD) approach is used to support computation mobility throughout the mobile cloud environment. The approach is fully adaptive, goal-driven and transparent. By downward task migration, applications running on the cloud nodes can exploit or take control of special resources in mobile devices such as GPS and cameras. With a restorable MPI layer, task migrations of MPI parallel programs can happen between cloud nodes or be initiated from a mobile device. Our evaluation shows that SOD outperforms several existing migration mechanisms in terms of migration overhead and latency. All our techniques result in better resource utilization through task migrations among cloud nodes and mobile nodes.published_or_final_versionThe 2011 International Conference on Cloud and Service Computing (CSC), Hong Kong, China, 12-14 December 2011. In Proceedings of CSC, 2011, p. 103-11

Microbiological and health related perspectives of geophagia: An overview

Geophagia, which refers to the deliberate eating of soil, is considered to be a deviant eating disorder, a sequel to poverty and famine but could also be observed in the absence of hunger and in both scenarios may be associated with high degree of mortality and morbidity. The phenomenon has been reported to be common among pregnant women, lactating women, school children and people with psychiatric disorders. The microbiology of soil shows a broad diversity and functionality of soil microflora which impact variously on soil and its consumption. Soil microbes contribute immensely to the quality of soil and even determine soil types. Geophagia may be beneficial or harmful. Beneficial aspects include the use of kaolin to treat diarrhea, gastritis, colitis, enhancement of bioactivities and maintenance of normal intestinal flora by commensal flora found in soil. Clay or soil containing special constituents are valuable oral and topical antimicrobials as well as adsorbents of toxins. Microbiological underpinnings of geophagia include the ingestion of eggs of parasitic worms such as Ascaris lumbricoides, Trichuris trichiura with the health consequences. Highly toxigenic bacteria such as Clostridium perfringens, Clostridium tetani, Clostridium botulinum, the causative agents of gas gangrene, tetanus and botulism and other human pathogens may be ingested. It has also been postulated that indirect consumption of soil may pose serious health problems. For example, nitrate run-off and leaching from soil into water bodies may lead to eutrophication and colonization by toxic cyanobacteria with ripple medical effects such as gastroenteritis. Some general health implications of geophagia include association with iron deficiency and anemia, intestinal obstruction, constipation, peritonitis, dental damage, eclampsia, iron deficiency and even mortality. The interplay of factors involved in geophagia, though varied, intricate and researched may not have been fully elucidated. Further concerted efforts aimed at multidisciplinary research are warranted so as to address gaps in the corpus of knowledge on the important subject.Keywords: Geohelminths, geophagia, health, microorganisms, soilAfrican Journal of Biotechnology Vol. 9(19), pp. 5784-5791, 10 May, 201

Effect of pulsed methylprednisolone on pain, in patients with HTLV-1-associated myelopathy

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an immune mediated myelopathy caused by the human T-lymphotropic virus type 1 (HTLV-1). The efficacy of treatments used for patients with HAM/TSP is uncertain. The aim of this study is to document the efficacy of pulsed methylprednisolone in patients with HAM/TSP. Data from an open cohort of 26 patients with HAM/TSP was retrospectively analysed. 1g IV methylprednisolone was infused on three consecutive days. The outcomes were pain, gait, urinary frequency and nocturia, a range of inflammatory markers and HTLV-1 proviral load. Treatment was well tolerated in all but one patient. Significant improvements in pain were: observed immediately, unrelated to duration of disease and maintained for three months. Improvement in gait was only seen on Day 3 of treatment. Baseline cytokine concentrations did not correlate to baseline pain or gait impairment but a decrease in tumour necrosis factor-alpha (TNF-α) concentration after pulsed methylprednisolone was associated with improvements in both. Until compared with placebo, treatment with pulsed methylprednisolone should be offered to patients with HAM/TSP for the treatment of pain present despite regular analgesia

Cluster Computing with Single Thread Space

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Endothelial cell processing and alternatively spliced transcripts of factor VIII: potential implications for coagulation cascades and pulmonary hypertension.

BACKGROUND: Coagulation factor VIII (FVIII) deficiency leads to haemophilia A. Conversely, elevated plasma levels are a strong predictor of recurrent venous thromboemboli and pulmonary hypertension phenotypes in which in situ thromboses are implicated. Extrahepatic sources of plasma FVIII are implicated, but have remained elusive. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemistry of normal human lung tissue, and confocal microscopy, flow cytometry, and ELISA quantification of conditioned media from normal primary endothelial cells were used to examine endothelial expression of FVIII and coexpression with von Willebrand Factor (vWF), which protects secreted FVIII heavy chain from rapid proteloysis. FVIII transcripts predicted from database mining were identified by RT-PCR and sequencing. FVIII mAb-reactive material was demonstrated in CD31+ endothelial cells in normal human lung tissue, and in primary pulmonary artery, pulmonary microvascular, and dermal microvascular endothelial cells. In pulmonary endothelial cells, this protein occasionally colocalized with vWF, centered on Weibel Palade bodies. Pulmonary artery and pulmonary microvascular endothelial cells secreted low levels of FVIII and vWF to conditioned media, and demonstrated cell surface expression of FVIII and vWF Ab-reacting proteins compared to an isotype control. Four endothelial splice isoforms were identified. Two utilize transcription start sites in alternate 5 exons within the int22h-1 repeat responsible for intron 22 inversions in 40% of severe haemophiliacs. A reciprocal relationship between the presence of short isoforms and full-length FVIII transcript suggested potential splice-switching mechanisms. CONCLUSIONS/SIGNIFICANCE: The pulmonary endothelium is confirmed as a site of FVIII secretion, with evidence of synthesis, cell surface expression, and coexpression with vWF. There is complex alternate transcription initiation from the FVIII gene. These findings provide a framework for future research on the regulation and perturbation of FVIII synthesis, and of potential relevance to haemophilia, thromboses, and pulmonary hypertensive states

Cost effectiveness of daclatasvir/asunaprevir versus peginterferon/ribavirin and protease inhibitors for the treatment of hepatitis c genotype 1b Naïve patients in Chile

© 2015 Vargas et al. Introduction: Daclatasvir and Asunaprevir (DCV/ASV) have recently been approved for the treatment of chronic hepatitis C virus infection. In association, they are more effective and safer than previous available treatments, but more expensive. It is unclear if paying for the additional costs is an efficient strategy considering limited resources. Methods: A Markov model was built to estimate the expected costs in Chilean pesos (CL$) and converted to US dollars (US$) and benefits in quality adjusted life years (QALYs) in a hypothetic cohort of naive patients receiving DCV/ASV compared to protease inhibitors (PIs) and Peginterferon plus Ribavirin (PR). Efficacy was obtained from a mixed-treatment comparison study and costs were estimated from local sources. Utilities were obtained applying the EQ-5D survey to local patients and then valued with the Chilean tariff. A time horizon of 46 years and a discount rate of 3% for costs and outcomes was considered. The ICERs were estimated for a range of DCV/ASV prices. Deterministic and probabilistic sensitivity analyses were performed. Results: PIs were extendedly dominated by DCV/ASV. The ICER of DCV/ASV compared to PR was US$16,635/QALY at a total treatment price of US$ 77,419; US$11,581 /QALY at a price of US$ 58,065; US$6,375/QALY at a price of US$ 38,710; and US$1,364 /QALY at a price of US$ 19,355. The probability of cost-effectiveness at a price of US$38,710 was 91.6$ 19,355. Although the results are sensitive to certain parameters, the ICER did not increase above the suggested threshold of 1 GDP per capita. Conclusions: DCV/ASV can be considered cost-effective at any price of the range studied. These results provide decision makers useful information about the value of incorporating these drugs into the public Chilean healthcare system

Prolonged survival of patients receiving trastuzumab beyond disease progression for HER2 overexpressing metastatic breast cancer (MBC)

Background: The aim of this retrospective analysis was to evaluate the impact of trastuzumab-based regimens on the survival of patients with HER2-overexpressing metastatic breast cancer (MBC). The study specifically focussed on the influence of the continuation of trastuzumab-based treatment despite tumor progression on survival. Patients and Methods: Patients with HER2 overexpressing MBC were included in this retrospective analysis. HER2 overexpression was determined by the immunohistochemical staining score (DAKO Hercep Test (TM)). Trastuzumab was applied at a loading dose of 4 mg/kg and a maintenance dose of 2 mg/kg. Results: Among 136 HER2 overexpressing patients (DAKO score 3+), 66 patients received first-line trastuzumab, 47 patients received trastuzumab as second-line therapy and 23 patients received trastuzumab beyond disease progression. There was no significant difference regarding the duration of trastuzumab-based treatment (first-line: 29.5 weeks vs. second-line: 25 weeks). Moreover, there was no difference in the response rate (first-line: 37.9% vs. second-line: 35.7%) or the median survival (p = 0.47 log rank). Patients who received >= 2 trastuzumab-based regimens for MBC survived significantly longer compared to those who had received only 1 regimen (>= 2 regimens: 62.4 months vs. 1 regimen: 38.5 months; p = 0.01 log rank). Conclusions: Trastuzumab is highly effective in the treatment of HER2 overexpressing MBC. Compared to historical controls, overall survival appears to be markedly prolonged, particularly in patients who received sequential trastuzumab-based treatment beyond disease progression

Probiotic administration in congenital heart disease: a pilot study.

ObjectiveTo investigate the impact of probiotic Bifidobacterium longum ssp. infantis on the fecal microbiota and plasma cytokines in neonates with congenital heart disease.Study designSixteen infants with congenital heart disease were randomly assigned to receive either B. infantis (4.2 × 10(9) colony-forming units two times daily) or placebo for 8 weeks. Stool specimens from enrolled infants and from six term infants without heart disease were analyzed for microbial composition. Plasma cytokines were analyzed weekly in the infants with heart disease.ResultsHealthy control infants had increased total bacteria, total Bacteroidetes and total bifidobacteria compared to the infants with heart disease, but there were no significant differences between the placebo and probiotic groups. Plasma interleukin (IL)10, interferon (IFN)γ and IL1β levels were transiently higher in the probiotic group.ConclusionCongenital heart disease in infants is associated with dysbiosis. Probiotic B. infantis did not significantly alter the fecal microbiota. Alterations in plasma cytokines were found to be inconsistent

A survey of indigenous herbal diarrhoeal remedies of O.R. Tambo district, Eastern Cape Province, South Africa

Indigenous health system and the use of herbal plants have been recognized as pivotal in primary health care and a system to reckon with in achieving one of the targets of the millennial goals on health.An ethnobotanical survey was conducted to identify indigenous herbal remedies for diarrhoea and associated stomach ailments in rural areas of the O.R. Tambo district municipality in the Eastern Cape province of South Africa. The main objective of the study was to gather ethnomedical data onpotentially valuable indigenous medicinal plants for the eventual development of new pharmaceuticals and also emphasize the role of ethnomedicine in primary health care. The use of herbal remedies in thetreatment of diarrhoea and dysentery was investigated using interviews. The survey was conducted among traditional healers and knowledgeable local elders who use medicinal plants to treat common illnesses. Data from the survey indicated the names of plants commonly used in the treatment of diarrhoea and associated ailments, the methods of preparation, parts used and administration. A total of 32 plant species belonging to 26 families were reportedly used as diarrhoea remedy in the study area. The most predominant families of medicinal plants employed and most frequently recommended were Fabaceae (16.67%), followed by Hyacinthaceae and Hydnoraceae (8.33% each). The most commonly utilized portions of plants for medicinal purposes included roots and leaves. Other parts were corms, bulbs, tubers, fruits and bark. The methods of preparation often employed were decoctions and infusions whilst medication was frequently administered orally or as enema. Some of the plants were used singly or mixed with other plant(s) while some edible ones are consumed as food. The survey documented a diversity of plants employed as remedy for diarrhoea. Integration of this form of health care system into western medicine is warranted. The propagation of such medicinal plants is vital for sustainable use of these medicinal plants