Munchausen by internet: current research and future directions.

The Internet has revolutionized the health world, enabling self-diagnosis and online support to take place irrespective of time or location. Alongside the positive aspects for an individual's health from making use of the Internet, debate has intensified on how the increasing use of Web technology might have a negative impact on patients, caregivers, and practitioners. One such negative health-related behavior is Munchausen by Internet

A Research Agenda for Helminth Diseases of Humans: Health Research and Capacity Building in Disease-Endemic Countries for Helminthiases Control

Capacity building in health research generally, and helminthiasis research particularly, is pivotal to the implementation of the research and development agenda for the control and elimination of human helminthiases that has been proposed thematically in the preceding reviews of this collection. Since helminth infections affect human populations particularly in marginalised and low-income regions of the world, they belong to the group of poverty-related infectious diseases, and their alleviation through research, policy, and practice is a sine qua non condition for the achievement of the United Nations Millennium Development Goals. Current efforts supporting research capacity building specifically for the control of helminthiases have been devised and funded, almost in their entirety, by international donor agencies, major funding bodies, and academic institutions from the developed world, contributing to the creation of (not always equitable) North–South “partnerships”. There is an urgent need to shift this paradigm in disease-endemic countries (DECs) by refocusing political will, and harnessing unshakeable commitment by the countries' governments, towards health research and capacity building policies to ensure long-term investment in combating and sustaining the control and eventual elimination of infectious diseases of poverty. The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research and identify research priorities and gaps. This paper discusses the challenges confronting capacity building for parasitic disease research in DECs, describes current capacity building strategies with particular reference to neglected tropical diseases and human helminthiases, and outlines recommendations to redress the balance of alliances and partnerships for health research between the developed countries of the “North” and the developing countries of the “South”. We argue that investing in South–South collaborative research policies and capacity is as important as their North–South counterparts and is essential for scaled-up and improved control of helminthic diseases and ultimately for regional elimination

Fyn Mediates Leptin Actions in the Thymus of Rodents

BACKGROUND:Several effects of leptin in the immune system rely on its capacity to modulate cytokine expression and apoptosis in the thymus. Surprisingly, some of these effects are dependent on signal transduction through the IRS1/PI3-kinase, but not on the activation of JAK2. Since all the well known effects of leptin in different cell types and tissues seem to be dependent on JAK2 activation, we hypothesized that, at least for the control of thymic function, another, unknown kinase could mediate the transduction of the leptin signal from the ObR towards the IRS1/PI3-kinase signaling cascade. METHODOLOGY/PRINCIPAL FINDINGS:Here, by employing immunoblot, real-time PCR and flow citometry we show that the tyrosine kinase, Fyn, is constitutively associated with the ObR in thymic cells. Following a leptin stimulus, Fyn undergoes an activating tyrosine phosphorylation and a transient association with IRS1. All these effects are independent of JAK2 activation and, upon Fyn inhibition, the signal transduction towards IRS1/PI3-kinase is abolished. In addition, the inhibition of Fyn significantly modifies the effects of leptin on thymic cytokine expression. CONCLUSION/SIGNIFICANCE:Therefore, in the thymus, Fyn acts as a tyrosine kinase that transduces the leptin signal independently of JAK2 activation, and mediates some of the immunomodulatory effects of leptin in this tissue

Interactive effects of pesticide exposure and habitat structure on behavior and predation of a marine larval fish

Coastal development has generated multiple stressors in marine and estuarine ecosystems, including habitat degradation and pollutant exposure, but the effects of these stressors on the ecology of fishes remain poorly understood. We studied the separate and combined effects of an acute 4 h sublethal exposure of the pyrethroid pesticide esfenvalerate and structural habitat complexity on behavior and predation risk of larval topsmelt (Atherinops affinis). Larvae were exposed to four nominal esfenvalerate concentrations (control, 0.12, 0.59, 1.18 μg/L), before placement into 12 L mesocosms with a three-spine stickleback (Gasterosteus aculeatus) predator. Five treatments of artificial eelgrass included a (1) uniform and (2) patchy distribution of eelgrass at a low density (500 shoots per m(2)), a (3) uniform and (4) patchy distribution of eelgrass at a high density (1,000 shoots per m(2)), and (5) the absence of eelgrass. The capture success of predators and aggregative behavior of prey were observed in each mesocosm for 10 min of each trial, and mortality of prey was recorded after 60 min. Exposure to esfenvalerate increased the proportion of larvae with swimming abnormalities. Surprisingly, prey mortality did not increase linearly with pesticide exposure but increased with habitat structure (density of eelgrass), which may have been a consequence of compensating predator behavior. The degree of prey aggregation decreased with both habitat structure and pesticide exposure, suggesting that anti-predator behaviors by prey may have been hampered by the interactive effects of both of these factors

Nucleolus: the fascinating nuclear body

Nucleoli are the prominent contrasted structures of the cell nucleus. In the nucleolus, ribosomal RNAs are synthesized, processed and assembled with ribosomal proteins. RNA polymerase I synthesizes the ribosomal RNAs and this activity is cell cycle regulated. The nucleolus reveals the functional organization of the nucleus in which the compartmentation of the different steps of ribosome biogenesis is observed whereas the nucleolar machineries are in permanent exchange with the nucleoplasm and other nuclear bodies. After mitosis, nucleolar assembly is a time and space regulated process controlled by the cell cycle. In addition, by generating a large volume in the nucleus with apparently no RNA polymerase II activity, the nucleolus creates a domain of retention/sequestration of molecules normally active outside the nucleolus. Viruses interact with the nucleolus and recruit nucleolar proteins to facilitate virus replication. The nucleolus is also a sensor of stress due to the redistribution of the ribosomal proteins in the nucleoplasm by nucleolus disruption. The nucleolus plays several crucial functions in the nucleus: in addition to its function as ribosome factory of the cells it is a multifunctional nuclear domain, and nucleolar activity is linked with several pathologies. Perspectives on the evolution of this research area are proposed

Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment

Variation in the human genome is a most important cause of variable response to drugs and other xenobiotics. Susceptibility to almost all diseases is determined to some extent by genetic variation. Driven by the advances in molecular biology, pharmacogenetics has evolved within the past 40 years from a niche discipline to a major driving force of clinical pharmacology, and it is currently one of the most actively pursued disciplines in applied biomedical research in general. Nowadays we can assess more than 1,000,000 polymorphisms or the expression of more than 25,000 genes in each participant of a clinical study – at affordable costs. This has not yet significantly changed common therapeutic practices, but a number of physicians are starting to consider polymorphisms, such as those in CYP2C9, CYP2C19, CYP2D6, TPMT and VKORC1, in daily medical practice. More obviously, pharmacogenetics has changed the practices and requirements in preclinical and clinical drug research; large clinical trials without a pharmacogenomic add-on appear to have become the minority. This review is about how the discipline of pharmacogenetics has evolved from the analysis of single proteins to current approaches involving the broad analyses of the entire genome and of all mRNA species or all metabolites and other approaches aimed at trying to understand the entire biological system. Pharmacogenetics and genomics are becoming substantially integrated fields of the profession of clinical pharmacology, and education in the relevant methods, knowledge and concepts form an indispensable part of the clinical pharmacology curriculum and the professional life of pharmacologists from early drug discovery to pharmacovigilance

Mechanical, pH and Thermal Stability of Mesoporous Hydroxyapatite

The stability of mesoporous hydroxyapatite (HAP) powder was studied following treatments of ultrasound, pH and heating. HAP was found to be mechanically stable up to (and including) 1 h continuous ultrasonic treatment in water. The HAP structure was also stable to pH, evidenced by practically identical XRD and FTIR spectra over the pH range 2–12. The surface area increased progressively with increasing acidity, reaching a maximum of 121.9 m 2 g −1 at pH 2, while alkaline conditions decreased the surface area to a minimum of 55.4 m 2 g −1 at pH 12. Heating in air had a significant influence on the structural and morphological properties of HAP, which underwent dehydroxylation to form oxyhydroxyapatite (OHAP) at temperatures ≥ 650 °C, and β-tricalcium phosphate (β-TCP) ≥750 °C. The surface area decreased at elevated temperatures due to agglomeration of HAP crystals by sintering, which was associated with an increased particle size