Geographic information system (GIS) maps and malaria control monitoring: intervention coverage and health outcome in distal villages of Khammouane province, Laos

Abstract Background Insecticide-treated nets (ITNs) are a key intervention to control malaria. The intervention coverage varies as a consequence of geographical accessibility to remote villages and limitations of financial and human resources for the intervention. People's adherence to the intervention, i.e., proper use of ITNs, also affects malaria health outcome. The study objective is to explore the impact of the intervention coverage and people's adherence to the intervention on malaria health outcome among targeted villages in various geographic locations. Methods Geographic information system (GIS) maps were developed using the data collected in an active case detection survey in Khammouane province, Laos. The survey was conducted using rapid diagnostic tests (RDTs) and a structured questionnaire at 23 sites in the province from June to July, the rainy season, in 2005. A total of 1,711 villagers from 403 households participated in the survey. Results As indicated on the GIS maps, villages with malaria cases, lower intervention coverage, and lower adherence were identified. Although no malaria case was detected in most villages with the best access to the district center, several cases were detected in the distal villages, where the intervention coverage and adherence to the intervention remained relatively lower. Conclusion Based on the data and maps, it was demonstrated that malaria remained unevenly distributed within districts. Balancing the intervention coverage in the distal villages with the overall coverage and continued promotion of the proper use of ITNs are necessary for a further reduction of malaria cases in the province.</p

The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic β-cell line

A previously uncharacterized putative ion channel, NALCN (sodium leak channel, non-selective), has been recently shown to be responsible for the tetrodotoxin (TTX)-resistant sodium leak current implicated in the regulation of neuronal excitability. Here, we show that NALCN encodes a current that is activated by M3 muscarinic receptors (M3R) in a pancreatic β-cell line. This current is primarily permeant to sodium ions, independent of intracellular calcium stores and G proteins but dependent on Src activation, and resistant to TTX. The current is recapitulated by co-expression of NALCN and M3R in human embryonic kidney-293 cells and in Xenopus oocytes. We also show that NALCN and M3R belong to the same protein complex, involving the intracellular I–II loop of NALCN and the intracellular i3 loop of M3R. Taken together, our data show the molecular basis of a muscarinic-activated inward sodium current that is independent of G-protein activation, and provide new insights into the properties of NALCN channels

Fate specification and tissue-specific cell cycle control of the <i>Caenorhabditis elegans</i> intestine

Coordination between cell fate specification and cell cycle control in multicellular organisms is essential to regulate cell numbers in tissues and organs during development, and its failure may lead to oncogenesis. In mammalian cells, as part of a general cell cycle checkpoint mechanism, the F-box protein β-transducin repeat-containing protein (β-TrCP) and the Skp1/Cul1/F-box complex control the periodic cell cycle fluctuations in abundance of the CDC25A and B phosphatases. Here, we find that the Caenorhabditis elegans β-TrCP orthologue LIN-23 regulates a progressive decline of CDC-25.1 abundance over several embryonic cell cycles and specifies cell number of one tissue, the embryonic intestine. The negative regulation of CDC-25.1 abundance by LIN-23 may be developmentally controlled because CDC-25.1 accumulates over time within the developing germline, where LIN-23 is also present. Concurrent with the destabilization of CDC-25.1, LIN-23 displays a spatially dynamic behavior in the embryo, periodically entering a nuclear compartment where CDC-25.1 is abundant

A Mathematical Model of Mitotic Exit in Budding Yeast: The Role of Polo Kinase

Cell cycle progression in eukaryotes is regulated by periodic activation and inactivation of a family of cyclin–dependent kinases (Cdk's). Entry into mitosis requires phosphorylation of many proteins targeted by mitotic Cdk, and exit from mitosis requires proteolysis of mitotic cyclins and dephosphorylation of their targeted proteins. Mitotic exit in budding yeast is known to involve the interplay of mitotic kinases (Cdk and Polo kinases) and phosphatases (Cdc55/PP2A and Cdc14), as well as the action of the anaphase promoting complex (APC) in degrading specific proteins in anaphase and telophase. To understand the intricacies of this mechanism, we propose a mathematical model for the molecular events during mitotic exit in budding yeast. The model captures the dynamics of this network in wild-type yeast cells and 110 mutant strains. The model clarifies the roles of Polo-like kinase (Cdc5) in the Cdc14 early anaphase release pathway and in the G-protein regulated mitotic exit network

Claims about the Misuse of Insecticide-Treated Mosquito Nets: Are These Evidence-Based?

Thomas Eisele and colleagues dispute reports in the media and elsewhere that insecticide-treated nets are not widely used, or are misused, and say that such misconceptions are not evidence-based and are damaging to malaria control efforts

The HDAC inhibitor SAHA improves depressive-like behavior of CRTC1-deficient mice: Possible relevance for treatment-resistant depression.

Major depression is a highly complex disabling psychiatric disorder affecting millions of people worldwide. Despite the availability of several classes of antidepressants, a substantial percentage of patients are unresponsive to these medications. A better understanding of the neurobiology of depression and the mechanisms underlying antidepressant response is thus critically needed. We previously reported that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) exhibit a depressive-like phenotype and a blunted antidepressant response to the selective serotonin reuptake inhibitor fluoxetine. In this study, we similarly show that Crtc1(-/-) mice are resistant to the antidepressant effect of chronic desipramine in a behavioral despair paradigm. Supporting the blunted response to this tricyclic antidepressant, we found that desipramine does not significantly increase the expression of Bdnf and Nr4a1-3 in the hippocampus and prefrontal cortex of Crtc1(-/-) mice. Epigenetic regulation of neuroplasticity gene expression has been associated with depression and antidepressant response, and histone deacetylase (HDAC) inhibitors have been shown to have antidepressant-like properties. Here, we show that unlike conventional antidepressants, chronic systemic administration of the HDAC inhibitor SAHA partially rescues the depressive-like behavior of Crtc1(-/-) mice. This behavioral effect is accompanied by an increased expression of Bdnf, but not Nr4a1-3, in the prefrontal cortex of these mice, suggesting that this epigenetic intervention restores the expression of a subset of genes by acting downstream of CRTC1. These findings suggest that CRTC1 alterations may be associated with treatment-resistant depression, and support the interesting possibility that targeting HDACs may be a useful therapeutic strategy in antidepressant development

Acute symptomatic hypoglycaemia mimicking ischaemic stroke on imaging:a systemic review

<p>Abstract</p> <p>Background</p> <p>Acute symptomatic hypoglycaemia is a differential diagnosis in patients presenting with stroke-like neurological impairment, but few textbooks describe the full brain imaging appearances. We systematically reviewed the literature to identify how often hypoglycaemia may mimic ischaemic stroke on imaging, common patterns and relationships with hypoglycaemia severity, duration, clinical outcome and add two new cases.</p> <p>Methods</p> <p>We searched EMBASE and Medline databases for papers reporting imaging in adults with symptomatic hypoglycaemia. We analysed the clinical presentation, outcome, brain imaging findings, duration and severity of hypoglycaemia, time course of lesion appearance, including two new cases.</p> <p>Results</p> <p>We found 42 papers describing computed tomography or magnetic resonance imaging in 65 patients, plus our two cases with symptomatic hypoglycaemia. Imaging abnormalities on computed tomography and magnetic resonance were uni or bilateral, cortical or sub-cortical. Thirteen (20%) mimicked cortical or lacunar stroke. Acute lesions had restricted diffusion on magnetic resonance or low attenuation on computed tomography, plus swelling; older lesions showed focal atrophy or disappeared, as with ischaemic stroke. The association between the depth or duration of hypoglycaemia, the severity or extent of neurological deficit, and the imaging abnormalities, was weak.</p> <p>Conclusion</p> <p>Imaging abnormalities in patients with hypoglycaemia are uncommon but very variable, weakly associated with neurological deficit, and about a fifth mimic acute ischaemic stroke. Blood glucose testing should be routine in all patients with acute neurological impairment and hypoglycaemia should be included in the differential diagnosis of imaging appearances in patients presenting with acute stroke.</p

Effects of etizolam and ethyl loflazepate on the P300 event-related potential in healthy subjects

<p>Abstract</p> <p>Background</p> <p>Benzodiazepines carry the risk of inducing cognitive impairments, which may go unnoticed while profoundly disturbing social activity. Furthermore, these impairments are partly associated with the elimination half-life (EH) of the substance from the body. The object of the present study was to examine the effects of etizolam and ethyl loflazepate, with EHs of 6 h and 122 h, respectively, on information processing in healthy subjects.</p> <p>Methods</p> <p>Healthy people were administered etizolam and ethyl loflazepate acutely and subchronically (14 days). The auditory P300 event-related potential and the neuropsychological batteries described below were employed to assess the effects of drugs on cognition. The P300 event-related potential was recorded before and after drug treatments. The digit symbol test, trail making test, digit span test and verbal paired associates test were administered to examine mental slowing and memory functioning.</p> <p>Results</p> <p>Acute administration of drugs caused prolongation in P300 latency and reduction in P300 amplitude. Etizolam caused a statistically significant prolongation in P300 latency compared to ethyl loflazepate. Furthermore, subchronic administration of etizolam, but not ethyl loflazepate, still caused a weak prolongation in P300 latency. In contrast, neuropsychological tests showed no difference.</p> <p>Conclusions</p> <p>The results indicate that acute administration of ethyl loflazepate induces less effect on P300 latency than etizolam.</p

The opposite effects of fluvoxamine and sertraline in the treatment of psychotic major depression: a case report

<p>Abstract</p> <p>Background</p> <p>Psychotic major depression is a clinical subtype of major depressive disorder. A number of clinical studies have demonstrated the efficacy of the combination of an antidepressant (for example, a tricyclic antidepressant or selective serotonin reuptake inhibitor (SSRI)) and an atypical antipsychotic or electroconvulsive therapy (ECT) in treating psychotic major depression. In several studies, monotherapy of SSRIs such as fluvoxamine has been shown to be effective in the treatment of psychotic major depression.</p> <p>Methods</p> <p>We report on a 36-year-old Japanese woman in whom fluvoxamine (a SSRI with sigma-1 receptor agonist) and sertraline (a SSRI with sigma-1 receptor antagonist) showed the opposite effects on psychotic symptoms in the treatment of psychotic major depression.</p> <p>Results</p> <p>Symptoms of depression and psychosis in the patient who was non-respondent to antipsychotic drugs improved after fluvoxamine monotherapy. At 3 years later, a switch to sertraline from fluvoxamine dramatically worsened the psychotic symptoms in the patient. Then, a switch back to fluvoxamine from sertraline improved these symptoms 1 week after fluvoxamine treatment.</p> <p>Conclusion</p> <p>Doctors should consider the monotherapy of sigma-1 receptor agonist fluvoxamine as an alternative approach to treating psychotic major depression.</p