the complexity of host's effective immune response against a polymorphic parasitic disease

This review is aimed at providing a comprehensive outline of the immune response displayed against cutaneous leishmaniasis (CL), the more common zoonotic infection caused by protozoan parasites of the genus Leishmania. Although of polymorphic clinical presentation, classically CL is characterized by leishmaniotic lesions on the face and extremities of the patients, which can be ulcerative, and even after healing can lead to permanent injuries and disfigurement, affecting significantly their psychological, social, and economic well-being. According a report released by the World Health Organization, the disability-adjusted life years (DALYs) lost due to leishmaniasis are close to 2.4 million, annually there are 1.0-1.5 million new cases of CL, and a numerous population is at risk in the endemic areas. Despite its increasing worldwide incidence, it is one of the so-called neglected tropical diseases. Furthermore, this review provides an overview of the existing knowledge of the host innate and acquired immune response to cutaneous species of Leishmania. The use of animal models and of in vitro studies has improved the understanding of parasite-host interplay and the complexity of immune mechanisms involved. The importance of diagnosis accuracy associated with effective patient management in CL reduction is highlighted. However, the multiple factors involved in CL epizoology associated with the unavailability of vaccines or drugs to prevent infection make difficult to formulate an effective strategy for CL control.publishersversionpublishe

from in uterus to elderly

Immune system recognize and fight back foreign microorganisms and inner modifications that lead to deficient cell and tissue functions. During a dog's life, the immune system needs to adapt to different physiological conditions, assuring surveillance and protection in a careful and controlled way. Pregnancy alters normal homeostasis, requiring a balance between immunity and tolerance. The embryos and fetus should be protected from infections, while the female dog must tolerate the growing of semi-allografts in her uterus. After birth, newborn puppies are at great risk of developing infectious diseases, because their immune system is in development and immune memory is absent. Passive transfer of immunity through colostrum is fundamental for puppy survival in the first weeks of life, but hampers the development of an active immune response to vaccination. At the end of life, dogs experience a decline in the structure and functional competence of the immune system, compromising the immune responses to novel antigenic challenges, such as infections and vaccines. Therefore, the current article reviews the general processes related to the development of the dog´s immune system, providing an overview of immune activity throughout the dog's life and its implications in canine health, and highlighting priority research goals.publishersversionpublishe

iDirac: a field-portable instrument for long-term autonomous measurements of isoprene and selected VOCs

The iDirac is a new instrument to measure selected hydrocarbons in the remote atmosphere. A robust design is central to its specifications, with portability, power efficiency, low gas consumption and autonomy as the other driving factors in the instrument development. The iDirac is a dual-column isothermal oven gas chromatograph with photoionisation detection (GC-PID). The instrument is designed and built in-house. It features a modular design, with the novel use of open-source technology for accurate instrument control. Currently configured to measure biogenic isoprene, the system is suitable for a range of compounds. For isoprene measurements in the field, the instrument precision (relative standard deviation) is ±10 %, with a limit of detection down to 38 pmol mol−1 (or ppt). The instrument was first tested in the field in 2015 during a ground-based campaign, and has since shown itself suitable for deployment in a variety of environments and platforms. This paper describes the instrument design, operation and performance based on laboratory tests in a controlled environment as well as during deployments in forests in Malaysian Borneo and central England

Successful treatment of feline leishmaniosis using an association of allopurinol and N-methyl-glucamine antimoniate

This work describes the diagnosis and successful treatment of a 2-year-old domestic cat infected with Leishmania species and presenting fever, and ulcerative and nodular skin lesions after being treated for pyodermatitis for 1 year without clinical improvement. After anamnesis the cat was submitted to a complete clinical examination. Blood was collected for determination of haematological and biochemical parameters, detection of feline leukaemia virus (FeLV), feline immunodeficiency virus (FIV), feline coronavirus (FCoV) and Leishmania amastigotes. Fine-needle aspiration puncture from the skin nodules was also performed. After definitive diagnosis the animal was treated and followed up over a 2 year period. The animal tested negative for FIV-specific antibodies, FeLV antigen and feline coronavirus RNA. Leishmania amastigotes in the skin nodules were confirmed by cytology and molecular diagnosis. Treatment was initiated with allopurinol, resulting in a slight clinical improvement. Thus, N-methyl-glucamine antimoniate was added and administered for 30 days, with complete closure of the ulcerative lesions in the hindlimbs requiring a surgical approach. Close monitoring of the patient in the following 24 months indicated that combined therapy was safe and clinical cure was achieved without further relapses or side effects.publishersversionpublishe

Filmmaking education and enterprise culture: an ethnographic exploration of two filmmaking education contexts and their relation to bedroom culture and the creative workplace

Filmmaking education has never been firmly integrated into schooling and in past years has suffered from cuts to funding for youth work and formal and non-formal arts education. It continues to exist only by drawing on creative industry and cultural consumption practices as well as state funding. In this paper we explore the filmmaking education contexts we encountered while doing our own pieces of year-long ethnographic research. These contexts import 'enterprising' ways of thinking, doing and being from the creative workplace and 'bedroom culture'. Located across life's domains, they address enterprising subjects who take pleasure in work, make use of leisure, and who are always learning. We argue that these filmmaking education contexts support young people to develop their private creative practice and introduce them to the possibility of work in the creative industries but, because of the enterprise culture in which they are entangled, uncritically address these young people as enterprising subjects

Phosphate Energy Metabolism During Domoic Acid-Induced Seizures

The effect of domoic acid-induced seizure activity on energy metabolism and on brain pH in mice was studied by continuous EEC recording and in vivo 31 P nuclear magnetic resonance (NMR) spectroscopy. Mice were divided into ventilated (n = 6) and nonventilated (n = 7) groups. Baseline EEG was 0.1-mV amplitude with frequence of >30-Hz and of 4–5 Hz. After intraperitoneal (i.p.) administration of domoic acid (6 mg/kg), electro graphic spikes appeared at increasing frequency, pro gressing to high-amplitude (0.1-0.8 mV) continuous sei zure activity (status epilepticus). In ventilated mice, the [ 31 P]NMR spectra showed that high-energy phosphate levels and tissue pH did not change after domoic acid administration or during the intervals of spiking or status epilepticus. Nonventilated mice showed periods of EEG suppression accompanied by decreases in the levels of high-energy phosphate metabolites and in pH, corresponding to episodic respiratory suppression during the spiking interval. In all animals, status epilepticus was fol lowed by a marked decrease in EEG amplitude that pro gressed rapidly to isoelectric silence. [ 31 P]NMR spectra obtained after this were indicative of total energy failure and tissue acidosis. In a separate group of ventilated mice (n = 4), domoic acid-induced status epilepticus was ac companied initially by an increase in mean arterial blood pressure (MAP) that slowly returned to baseline level. Isoelectric silence was accompanied by a decrease in MAP to 75 ± 8 mm Hg. These experiments suggest that domoic acid-induced seizures are not accompanied by an increase in substrate demand that exceeds supply.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65953/1/j.1528-1157.1993.tb02124.x.pd

The collagen receptor discoidin domain receptor 1b enhances integrin β1-mediated cell migration by interacting with talin and promoting Rac1 activation.

Integrins and discoidin domain receptors (DDRs) 1 and 2 promote cell adhesion and migration on both fibrillar and non fibrillar collagens. Collagen I contains DDR and integrin selective binding motifs; however, the relative contribution of these two receptors in regulating cell migration is unclear. DDR1 has five isoforms (DDR1a-e), with most cells expressing the DDR1a and DDR1b isoforms. We show that human embryonic kidney 293 cells expressing DDR1b migrate more than DDR1a expressing cells on DDR selective substrata as well as on collagen I in vitro. In addition, DDR1b expressing cells show increased lung colonization after tail vein injection in nude mice. DDR1a and DDR1b differ from each other by an extra 37 amino acids in the DDR1b cytoplasmic domain. Interestingly, these 37 amino acids contain an NPxY motif which is a central control module within the cytoplasmic domain of β integrins and acts by binding scaffold proteins, including talin. Using purified recombinant DDR1 cytoplasmic tail proteins, we show that DDR1b directly binds talin with higher affinity than DDR1a. In cells, DDR1b, but not DDR1a, colocalizes with talin and integrin β1 to focal adhesions and enhances integrin β1-mediated cell migration. Moreover, we show that DDR1b promotes cell migration by enhancing Rac1 activation. Mechanistically DDR1b interacts with the GTPase-activating protein (GAP) Breakpoint cluster region protein (BCR) thus reducing its GAP activity and enhancing Rac activation. Our study identifies DDR1b as a major driver of cell migration and talin and BCR as key players in the interplay between integrins and DDR1b in regulating cell migration

The Values of Tangible User Interfaces: How to discover, assess and evaluate them?

Since the introduction of Tangible User Interfaces, in the beginning of the 90s, a generation grew up interacting with computers. At the same time the context of computing changed dramatically: from a device used almost exclusively by specialists, it evolved to a general device that plays a dominant role in our societies. But where does this leave TUI? In many respects, the idea of tangibility plays a marginal role in Human Computer Interaction. It makes sense to re-evaluate the intrinsic values of TUI design. This paper proposes to research the appropriate metrics to do so

The effect of a clinical pharmacist discharge service on medication discrepancies in patients with heart failure

Objective: Heart failure patients are regularly admitted to hospital and frequently use multiple medication. Besides intentional changes in pharmacotherapy, unintentional changes may occur during hospitalisation. The aim of this study was to investigate the effect of a clinical pharmacist discharge service on medication discrepancies and prescription errors in patients with heart failure. Setting: A general teaching hospital in Tilburg, the Netherlands. Method: An open randomized intervention study was performed comparing an intervention group, with a control group receiving regular care by doctors and nurses. The clinical pharmacist discharge service consisted of review of discharge medication, communicating prescribing errors with the cardiologist, giving patients information, preparation of a written overview of the discharge medication and communication to both the community pharmacist and the general practitioner about this medication. Within 6 weeks after discharge all patients were routinely scheduled to visit the outpatient clinic and medication discrepancies were measured. Main outcome measure: The primary endpoint was the frequency of prescription errors in the discharge medication and medication discrepancies after discharge combined. Results: Forty-four patients were included in the control group and 41 in the intervention group. Sixty-eight percent of patients in the control group had at least one discrepancy or prescription error against 39% in the intervention group (RR 0.57 (95% CI 0.37-0.88)). The percentage of medications with a discrepancy or prescription error in the control group was 14.6% and in the intervention group it was 6.1% (RR 0.42 (95% CI 0.27-0.66)). Conclusion: This clinical pharmacist discharge service significantly reduces the risk of discrepancies and prescription errors in medication of patients with heart failure in the 1st month after discharge