Renal impairment in a rural African antiretroviral programme

Background: There is little knowledge regarding the prevalence and nature of renal impairment in African populations initiating antiretroviral treatment, nor evidence to inform the most cost effective methods of screening for renal impairment. With the increasing availability of the potentially nephrotixic drug, tenofovir, such information is important for the planning of antiretroviral programmes Methods: (i) Retrospective review of the prevalence and risk factors for impaired renal function in 2189 individuals initiating antiretroviral treatment in a rural African setting between 2004 and 2007 (ii) A prospective study of 149 consecutive patients initiating antiretrovirals to assess the utility of urine analysis for the detection of impaired renal function. Severe renal and moderately impaired renal function were defined as an estimated GFR of ≤ 30 mls/min/1.73 m2 and 30–60 mls/min/1.73 m2 respectively. Logistic regression was used to determine odds ratio (OR) of significantly impaired renal function (combining severe and moderate impairment). Co-variates for analysis were age, sex and CD4 count at initiation. Results: (i) There was a low prevalence of severe renal impairment (29/2189, 1.3% 95% C.I. 0.8–1.8) whereas moderate renal impairment was more frequent (287/2189, 13.1% 95% C.I. 11.6–14.5) with many patients having advanced immunosuppression at treatment initiation (median CD4 120 cells/μl). In multivariable logistic regression age over 40 (aOR 4.65, 95% C.I. 3.54–6.1), male gender (aOR 1.89, 95% C.I. 1.39–2.56) and CD4<100 cells/ul (aOR 1.4, 95% C.I. 1.07–1.82) were associated with risk of significant renal impairment (ii) In 149 consecutive patients, urine analysis had poor sensitivity and specificity for detecting impaired renal function. Conclusion: In this rural African setting, significant renal impairment is uncommon in patients initiating antiretrovirals. Urine analysis alone may be inadequate for identification of those with impaired renal function where resources for biochemistry are limited

A Geological Itinerary Through the Southern Apennine Thrust-Belt (Basilicata—Southern Italy)

Open access via Springer Compact AgreementPeer reviewedPublisher PD

Thiopentone sedation for sedation of acutely agitated, violent, intoxicated patients: Evaluation of 2 cases

Two cases of violent, drug-intoxicated patients who presented considerable problems in management, and were resistant to standard sedative agents, are described. Effective and safe sedation, without the need for full anaesthesia and endotracheal intubation, was achieved using titrated doses of thiopentone. The merits of selecting this agent in these circumstances are discussed

Tectono-stratigraphic evolution and crustal architecture of the Orphan Basin during North Atlantic rifting

The Orphan Basin is located in the deep offshore of the Newfoundland margin, and it is bounded by the continental shelf to the west, the Grand Banks to the south, and the continental blocks of Orphan Knoll and Flemish Cap to the east. The Orphan Basin formed in Mesozoic time during the opening of the North Atlantic Ocean between eastern Canada and western Iberia–Europe. This work, based on well data and regional seismic reflection profiles across the basin, indicates that the continental crust was affected by several extensional episodes between the Jurassic and the Early Cretaceous, separated by events of uplift and erosion. The preserved tectono-stratigraphic sequences in the basin reveal that deformation initiated in the eastern part of the Orphan Basin in the Jurassic and spread towards the west in the Early Cretaceous, resulting in numerous rift structures filled with a Jurassic–Lower Cretaceous syn-rift succession and overlain by thick Upper Cretaceous to Cenozoic post-rift sediments. The seismic data show an extremely thinned crust (4–16 km thick) underneath the eastern and western parts of the Orphan Basin, forming two sub-basins separated by a wide structural high with a relatively thick crust (17 km thick). Quantifying the crustal architecture in the basin highlights the large discrepancy between brittle extension localized in the upper crust and the overall crustal thinning. This suggests that continental deformation in the Orphan Basin involved, in addition to the documented Jurassic and Early Cretaceous rifting, an earlier brittle rift phase which is unidentifiable in seismic data and a depth-dependent thinning of the crust driven by localized lower crust ductile flow

Microglial activation and chronic neurodegeneration

Microglia, the resident innate immune cells in the brain, have long been implicated in the pathology of neurode-generative diseases. Accumulating evidence points to activated microglia as a chronic source of multiple neurotoxic factors, including tumor necrosis factor-α, nitric oxide, interleukin-1β, and reactive oxygen species (ROS), driving progressive neuron damage. Microglia can become chronically activated by either a single stimulus (e.g., lipopolysaccharide or neuron damage) or multiple stimuli exposures to result in cumulative neuronal loss with time. Although the mechanisms driving these phenomena are just beginning to be understood, reactive microgliosis (the microglial response to neuron damage) and ROS have been implicated as key mechanisms of chronic and neurotoxic microglial activation, particularly in the case of Parkinson’s disease. We review the mechanisms of neurotoxicity associated with chronic microglial activation and discuss the role of neuronal death and microglial ROS driving the chronic and toxic microglial phenotype

Understanding practice: the factors that influence management of mild traumatic brain injury in the emergency department-a qualitative study using the Theoretical Domains Framework

Background: Mild traumatic brain injury is a frequent cause of presentation to emergency departments. Despite the availability of clinical practice guidelines in this area, there is variation in practice. One of the aims of the Neurotrauma Evidence Translation program is to develop and evaluate a targeted, theory- and evidence-informed intervention to improve the management of mild traumatic brain injury in Australian emergency departments. This study is the first step in the intervention development process and uses the Theoretical Domains Framework to explore the factors perceived to influence the uptake of four key evidence-based recommended practices for managing mild traumatic brain injury. Methods: Semi-structured interviews were conducted with emergency staff in the Australian state of Victoria. The interview guide was developed using the Theoretical Domains Framework to explore current practice and to identify the factors perceived to influence practice. Two researchers coded the interview transcripts using thematic content analysis. Results: A total of 42 participants (9 Directors, 20 doctors and 13 nurses) were interviewed over a seven-month period. The results suggested that (i) the prospective assessment of post-traumatic amnesia was influenced by: knowledge; beliefs about consequences; environmental context and resources; skills; social/professional role and identity; and beliefs about capabilities; (ii) the use of guideline-developed criteria or decision rules to inform the appropriate use of a CT scan was influenced by: knowledge; beliefs about consequences; environmental context and resources; memory, attention and decision processes; beliefs about capabilities; social influences; skills and behavioral regulation; (iii) providing verbal and written patient information on discharge was influenced by: beliefs about consequences; environmental context and resources; memory, attention and decision processes; social/professional role and identity; and knowledge; (iv) the practice of providing brief, routine follow-up on discharge was influenced by: environmental context and resources; social/professional role and identity; knowledge; beliefs about consequences; and motivation and goals. Conclusions: Using the Theoretical Domains Framework, factors thought to influence the management of mild traumatic brain injury in the emergency department were identified. These factors present theoretically based targets for a future intervention

Effects of ranolazine on astrocytes and neurons in primary culture

Ranolazine (Rn) is an antianginal agent used for the treatment of chronic angina pectoris when angina is not adequately controlled by other drugs. Rn also acts in the central nervous system and it has been proposed for the treatment of pain and epileptic disorders. Under the hypothesis that ranolazine could act as a neuroprotective drug, we studied its effects on astrocytes and neurons in primary culture. We incubated rat astrocytes and neurons in primary cultures for 24 hours with Rn (10−7, 10−6 and 10−5 M). Cell viability and proliferation were measured using trypan blue exclusion assay, MTT conversion assay and LDH release assay. Apoptosis was determined by Caspase 3 activity assay. The effects of Rn on proinflammatory mediators IL-β and TNF-α was determined by ELISA technique, and protein expression levels of Smac/Diablo, PPAR-γ, Mn-SOD and Cu/Zn-SOD by western blot technique. In cultured astrocytes, Rn significantly increased cell viability and proliferation at any concentration tested, and decreased LDH leakage, Smac/Diablo expression and Caspase 3 activity indicating less cell death. Rn also increased anti-inflammatory PPAR-γ protein expression and reduced pro-inflammatory proteins IL-1 β and TNFα levels. Furthermore, antioxidant proteins Cu/Zn-SOD and Mn-SOD significantly increased after Rn addition in cultured astrocytes. Conversely, Rn did not exert any effect on cultured neurons. In conclusion, Rn could act as a neuroprotective drug in the central nervous system by promoting astrocyte viability, preventing necrosis and apoptosis, inhibiting inflammatory phenomena and inducing anti-inflammatory and antioxidant agents

Characterization of a fluvial aquifer at a range of depths and scales: the Triassic St Bees Sandstone Formation, Cumbria, UK

Fluvial sedimentary successions represent porous media that host groundwater and geothermal resources. Additionally, they overlie crystalline rocks hosting nuclear waste repositories in rift settings. The permeability characteristics of an arenaceous fluvial succession, the Triassic St Bees Sandstone Formation in England (UK), are described, from core-plug to well-test scale up to ~1 km depth. Within such lithified successions, dissolution associated with the circulation of meteoric water results in increased permeability (K~10−1–100 m/day) to depths of at least 150 m below ground level (BGL) in aquifer systems that are subject to rapid groundwater circulation. Thus, contaminant transport is likely to occur at relatively high rates. In a deeper investigation (> 150 m depth), where the aquifer has not been subjected to rapid groundwater circulation, well-test-scale hydraulic conductivity is lower, decreasing from K~10−2 m/day at 150–400 m BGL to 10−3 m/day down-dip at ~1 km BGL, where the pore fluid is hypersaline. Here, pore-scale permeability becomes progressively dominant with increasing lithostatic load. Notably, this work investigates a sandstone aquifer of fluvial origin at investigation depths consistent with highly enthalpy geothermal reservoirs (~0.7–1.1 km). At such depths, intergranular flow dominates in unfaulted areas with only minor contribution by bedding plane fractures. However, extensional faults represent preferential flow pathways, due to presence of high connective open fractures. Therefore, such faults may (1) drive nuclear waste contaminants towards the highly permeable shallow (< 150 m BGL) zone of the aquifer, and (2) influence fluid recovery in geothermal fields

Loss and Recovery Potential of Marine Habitats: An Experimental Study of Factors Maintaining Resilience in Subtidal Algal Forests at the Adriatic Sea

BACKGROUND: Predicting and abating the loss of natural habitats present a huge challenge in science, conservation and management. Algal forests are globally threatened by loss and severe recruitment failure, but our understanding of resilience in these systems and its potential disruption by anthropogenic factors lags well behind other habitats. We tested hypotheses regarding triggers for decline and recovery potential in subtidal forests of canopy-forming algae of the genus Cystoseira. METHODOLOGY/PRINCIPAL FINDINGS: By using a combination of historical data, and quantitative in situ observations of natural recruitment patterns we suggest that recent declines of forests along the coasts of the north Adriatic Sea were triggered by increasing cumulative impacts of natural- and human-induced habitat instability along with several extreme storm events. Clearing and transplantation experiments subsequently demonstrated that at such advanced stages of ecosystem degradation, increased substratum stability would be essential but not sufficient to reverse the loss, and that for recovery to occur removal of the new dominant space occupiers (i.e., opportunistic species including turf algae and mussels) would be required. Lack of surrounding adult canopies did not seem to impair the potential for assisted recovery, suggesting that in these systems recovery could be actively enhanced even following severe depletions. CONCLUSIONS/SIGNIFICANCE: We demonstrate that sudden habitat loss can be facilitated by long term changes in the biotic and abiotic conditions in the system, that erode the ability of natural ecosystems to absorb and recover from multiple stressors of natural and human origin. Moreover, we demonstrate that the mere restoration of environmental conditions preceding a loss, if possible, may be insufficient for ecosystem restoration, and is scarcely cost-effective. We conclude that the loss of complex marine habitats in human-dominated landscapes could be mitigated with appropriate consideration and management of incremental habitat changes and of attributes facilitating system recovery

Abnormal cortical responses to somatosensory stimulation in medication-overuse headache

BACKGROUND: Medication-overuse headache (MOH) is a frequent, disabling disorder. Despite a controversial pathophysiology convincing evidence attributes a pivotal role to central sensitization. Most patients with MOH initially have episodic migraine without aura (MOA) characterized interictally by an absent amplitude decrease in cortical evoked potentials to repetitive stimuli (habituation deficit), despite a normal initial amplitude (lack of sensitization). Whether central sensitization alters this electrophysiological profile is unknown. We therefore sought differences in somatosensory evoked potential (SEP) sensitization and habituation in patients with MOH and episodic MOA. METHODS: We recorded median-nerve SEPs (3 blocks of 100 sweeps) in 29 patients with MOH, 64 with MOA and 42 controls. Episodic migraineurs were studied during and between attacks. We measured N20-P25 amplitudes from 3 blocks of 100 sweeps, and assessed sensitization from block 1 amplitude, and habituation from amplitude changes between the 3 sequential blocks. RESULTS: In episodic migraineurs, interictal SEP amplitudes were normal in block 1, but thereafter failed to habituate. Ictal SEP amplitudes increased in block 1, then habituated normally. Patients with MOH had larger-amplitude block 1 SEPs than controls, and also lacked SEP habituation. SEP amplitudes were smaller in triptan overusers than in patients overusing nonsteroidal anti-inflammatory drugs (NSAIDs) or both medications combined, lowest in patients with the longest migraine history, and highest in those with the longest-lasting headache chronification. CONCLUSIONS: In patients with MOH, especially those overusing NSAIDs, the somatosensory cortex becomes increasingly sensitized. Sensory sensitization might add to the behavioral sensitization that favors compulsive drug intake, and may reflect drug-induced changes in central serotoninergic transmission