Platelet-Induced Clumping of Plasmodium falciparum–Infected Erythrocytes from Malawian Patients with Cerebral Malaria—Possible Modulation In Vivo by Thrombocytopenia

Platelets may play a role in the pathogenesis of human cerebral malaria (CM), and they have been shown to induce clumping of Plasmodium falciparum–parasitized red blood cells (PRBCs) in vitro. Both thrombocytopenia and platelet-inducedPRBCclumping are associated with severe malaria and, especially, withCM.In the present study, we investigated the occurrence of the clumping phenomenon in patients with CM by isolating and coincubating their plasma and PRBCs ex vivo. Malawian children with CM all had low platelet counts, with the degree of thrombocytopenia directly proportional to the density of parasitemia. Plasma samples obtained from these patients subsequently induced weak PRBC clumping. When the assays were repeated, with the plasma platelet concentrations adjusted to within the physiological range considered to be normal, massive clumping occurred. The results of this study suggest that thrombocytopenia may, through reduction of platelet-mediated clumping of PRBCs, provide a protective mechanism for the host during CM

New ophthalmosaurid ichthyosaurs from the European lower cretaceous demonstrate extensive ichthyosaur survival across the Jurassic–Cretaceous boundary

Background Ichthyosauria is a diverse clade of marine amniotes that spanned most of the Mesozoic. Until recently, most authors interpreted the fossil record as showing that three major extinction events affected this group during its history: one during the latest Triassic, one at the Jurassic–Cretaceous boundary (JCB), and one (resulting in total extinction) at the Cenomanian-Turonian boundary. The JCB was believed to eradicate most of the peculiar morphotypes found in the Late Jurassic, in favor of apparently less specialized forms in the Cretaceous. However, the record of ichthyosaurs from the Berriasian–Barremian interval is extremely limited, and the effects of the end-Jurassic extinction event on ichthyosaurs remains poorly understood. Methodology/Principal Findings Based on new material from the Hauterivian of England and Germany and on abundant material from the Cambridge Greensand Formation, we name a new ophthalmosaurid, Acamptonectes densus gen. et sp. nov. This taxon shares numerous features with Ophthalmosaurus, a genus now restricted to the Callovian–Berriasian interval. Our phylogenetic analysis indicates that Ophthalmosauridae diverged early in its history into two markedly distinct clades, Ophthalmosaurinae and Platypterygiinae, both of which cross the JCB and persist to the late Albian at least. To evaluate the effect of the JCB extinction event on ichthyosaurs, we calculated cladogenesis, extinction, and survival rates for each stage of the Oxfordian–Barremian interval, under different scenarios. The extinction rate during the JCB never surpasses the background extinction rate for the Oxfordian–Barremian interval and the JCB records one of the highest survival rates of the interval. Conclusions/Significance There is currently no evidence that ichthyosaurs were affected by the JCB extinction event, in contrast to many other marine groups. Ophthalmosaurid ichthyosaurs remained diverse from their rapid radiation in the Middle Jurassic to their total extinction at the beginning of the Late Cretaceous

MRSA model of learning and adaptation: a qualitative study among the general public

<p>Abstract</p> <p>Background</p> <p>More people in the US now die from Methicillin Resistant <it>Staphylococcus aureus </it>(MRSA) infections than from HIV/AIDS. Often acquired in healthcare facilities or during healthcare procedures, the extremely high incidence of MRSA infections and the dangerously low levels of literacy regarding antibiotic resistance in the general public are on a collision course. Traditional medical approaches to infection control and the conventional attitude healthcare practitioners adopt toward public education are no longer adequate to avoid this collision. This study helps us understand how people acquire and process new information and then adapt behaviours based on learning.</p> <p>Methods</p> <p>Using constructivist theory, semi-structured face-to-face and phone interviews were conducted to gather pertinent data. This allowed participants to tell their stories so their experiences could deepen our understanding of this crucial health issue. Interview transcripts were analysed using grounded theory and sensitizing concepts.</p> <p>Results</p> <p>Our findings were classified into two main categories, each of which in turn included three subthemes. First, in the category of <it>Learning</it>, we identified how individuals used their <it>Experiences with MRSA</it>, to answer the questions: <it>What was learned? </it>and, <it>How did learning occur? </it>The second category, <it>Adaptation </it>gave us insights into <it>Self-reliance, Reliance on others</it>, and <it>Reflections on the MRSA journey</it>.</p> <p>Conclusions</p> <p>This study underscores the critical importance of educational programs for patients, and improved continuing education for healthcare providers. Five specific results of this study can reduce the vacuum that currently exists between the knowledge and information available to healthcare professionals, and how that information is conveyed to the public. These points include: 1) a common model of MRSA learning and adaptation; 2) the self-directed nature of adult learning; 3) the focus on general MRSA information, care and prevention, and antibiotic resistance; 4) the interconnected nature of adaptation; and, 5) the need for a consistent step by step plan to deal with MRSA provided at the time of diagnosis.</p

Sympathomimetic effects of chronic methamphetamine abuse on oral health: a cross-sectional study

Background: Methamphetamine, a highly addictive sympathomimetic stimulant, is currently widely abused worldwide and has been associated with devastating effects on oral health, resulting in the term "meth mouth". However, "meth mouth" pathology is primarily based on case reports with a lack of systematic clinical evaluation. Therefore, we have conducted a systematic study to investigate (1) the pharmacological impact of methamphetamine on oral health with regard to saliva function, including the parameters saliva flow rate and total saliva production (ml/5 min) and the buffering capacity of saliva;(2) the contribution of the symptoms of bruxism and muscle trismus to potential oral health damage. Methods: We assessed the data of 100 chronic methamphetamine abusers and 100 matched-pair comparison participants. Primarily, we conducted an anamnesis with all methamphetamine abusers with regard to saliva dysfunctions, jaw clenching and pain in the temporomandibular joint. Subsequently, in the first part of the clinical enquiry, we tested the saliva flow rate and the total saliva production (ml/5 min) by using the sialometry method and the buffer capacity of saliva by determining the pH-value. In the second part of the clinical enquiry, we evaluated bruxism symptoms with respect to generalized tooth attrition, dentine exposure and visible enamel cracks and examined a potential muscle trismus by measuring the maximal opening of the mouth. Results: The majority of methamphetamine abusers reported a dry mouth (72 %) and jaw clenching (68 %). Almost half of all methamphetamine abusers experienced pain in the temporomandibular joint (47 %). With regard to the clinical findings, methamphetamine abusers showed significantly lower total saliva production (ml/5 min) (p 0.05). Conclusions: The sympathomimetic effects of chronic methamphetamine abuse may lead to dry mouth and extensive bruxism and therefore can increase the risk for caries decay, periodontal lesions and tooth wear. Furthermore, a significant decline of saliva buffer capacity in methamphetamine abusers may trigger the risk for dental erosions. Methamphetamine abusers and practitioners should be aware of these symptoms

Standard errors and confidence intervals in within-subjects designs: Generalizing Loftus and Masson (1994) and avoiding the biases of alternative accounts

Repeated measures designs are common in experimental psychology. Because of the correlational structure in these designs, the calculation and interpretation of confidence intervals is nontrivial. One solution was provided by Loftus and Masson (Psychonomic Bulletin & Review 1:476–490, 1994). This solution, although widely adopted, has the limitation of implying same-size confidence intervals for all factor levels, and therefore does not allow for the assessment of variance homogeneity assumptions (i.e., the circularity assumption, which is crucial for the repeated measures ANOVA). This limitation and the method’s perceived complexity have sometimes led scientists to use a simplified variant, based on a per-subject normalization of the data (Bakeman & McArthur, Behavior Research Methods, Instruments, & Computers 28:584–589, 1996; Cousineau, Tutorials in Quantitative Methods for Psychology 1:42–45, 2005; Morey, Tutorials in Quantitative Methods for Psychology 4:61–64, 2008; Morrison & Weaver, Behavior Research Methods, Instruments, & Computers 27:52–56, 1995). We show that this normalization method leads to biased results and is uninformative with regard to circularity. Instead, we provide a simple, intuitive generalization of the Loftus and Masson method that allows for assessment of the circularity assumption

Do semantic standards lack quality? : a survey among 34 semantic standards

The adoption of standards to improve interoperability in the automotive, aerospace, shipbuilding and other sectors could save billions. While interoperability standards have been created for a number of industries, problems persist, suggesting a lack of quality of the standards themselves. The issue of semantic standard quality is not often addressed. In this research we take a closer look at the quality of semantics standards, development processes, and survey the current state of the quality of semantic standards by means of a questionnaire that was sent to standards developers. This survey looked at 34 semantic standards, and it shows that the quality of semantic standards for inter-organizational interoperability can be improved. Improved standards may advance interoperability in networked business. Improvement of semantic standards requires transparency of their quality. Although many semantic standard development organisations already have quality assurance in place, this research shows that they could benefit from a quality measuring instrument

The global extent of biodiversity offset implementation under no net loss policies

‘No net loss’ (NNL) biodiversity policies, which seek to neutralize ongoing biodiversity losses caused by economic development activities, are applicable worldwide. Yet there has been no global assessment concerning practical measures actually implemented under NNL policies. Here, we systematically map the global implementation of biodiversity offsets (‘offsets’) – a crucial yet controversial NNL practice. We find, firstly, that offsets occupy an area up to two orders of magnitude larger than previously suggested: 12,983 offset projects extending over ?153,679?_(-64,223)^(+25,013) km2 across 37 countries. Secondly, offsets are far from homogeneous in implementation, and emerging economies (particularly in South America) are more dominant in terms of global offsetting area than expected. Thirdly, most offset projects are very small, and the overwhelming majority (99.7%) arise through regulatory requirements rather than prominent project finance safeguards. Our database provides a sampling frame via which future studies could evaluate the efficacy of NNL policies

The renal cortical interstitium: morphological and functional aspects

The renal interstitial compartment, situated between basement membranes of epithelia and vessels, contains two contiguous cellular networks. One network is formed by interstitial fibroblasts, the second one by dendritic cells. Both are in intimate contact with each other. Fibroblasts are interconnected by junctions and connected to basement membranes of vessels and tubules by focal adhesions. Fibroblasts constitute the “skeleton” of the kidney. In the renal cortex, fibroblasts produce erythropoietin and are distinguished from other interstitial cells by their prominent F-actin cytoskeleton, abundance of rough endoplasmic reticulum, and by ecto-5′-nucleotidase expression in their plasma membrane. The resident dendritic cells belong to the mononuclear phagocyte system and fulfil a sentinel function. They are characterized by their expression of MHC class II and CD11c. The central situation of fibroblasts suggests that signals from tubules, vessels, and inflammatory cells converge in fibroblasts and elicit an integrated response. Following tubular damage and inflammatory signals fibroblasts proliferate, change to the myofibroblast phenotype and increase their collagen production, potentially resulting in renal fibrosis. The acquisition of a profibrotic phenotype by fibroblasts in renal diseases is generally considered a main causal event in the progression of chronic renal failure. However, it might also be seen as a repair process

Workdays, in-between workdays and the weekend: a diary study on effort and recovery

Contains fulltext : 55892.pdf (publisher's version ) (Closed access)16 p

PDK-1 regulates lactate production in hypoxia and is associated with poor prognosis in head and neck squamous cancer

Here we describe the expression and function of a HIF-1-regulated protein pyruvate dehydrogenase kinase-1 (PDK-1) in head and neck squamous cancer (HNSCC). Using RNAi to downregulate hypoxia-inducible PDK-1, we found that lactate and pyruvate excretion after 16–48 h of hypoxia was suppressed to normoxic levels. This indicates that PDK-1 plays an important role in maintaining glycolysis. Knockdown had no effect on proliferation or survival under hypoxia. The immunohistochemical expression of PDK-1 was assessed in 140 cases of HNSCC. PDK-1 expression was not expressed in normal tissues but was upregulated in HNSCC and found to be predominantly cytoplasmic with occasional strong focal nuclear expression. It was strongly related to poor outcome (P=0.005 split by median). These results indicate that HIF regulation of PDK-1 has a key role in maintaining lactate production in human cancer and that the investigation of PDK-1 inhibitors should be investigated for antitumour effects