Survey of Philornis (Diptera: Muscidae) larvae in adult birds from central Argentina.

The majority of known Philornis species (Diptera: Muscidae) cause subcutaneous myiasis in Neotropical altricial and semi-altricial nestlings. Generating information about these parasites is of relevance as they are a threat for the conservation of some wild bird species and also because they are an excellent model to study the ecology of host-parasite interactions. Although there are records of this parasitism in adult birds, the parasitic larvae are primarily associated with nestlings. However, systematic surveys including active search for larvae in older birds have been very scarce. Here we present results from a survey conducted along 6 years and encompassing a sample of 3029 subadult and adult birds in Santa Fe province, Argentina, where broods are frequently parasitised by the Philornis torquans complex. We found only one dipteran larva parasitising a greater thornbird. This larva was morphologically compatible with Philornis. Given the extremely low estimated prevalence (1/3029 = 0.03%), we conclude that the presence of larvae in subadult and adult birds is an extremely rare event in the studied bird community and that the species belonging to the P. torquans complex present in central Argentina are almost exclusively parasites of nestlings.

Hemolysate-mediated platelet aggregation: an additional risk mechanism contributing to thrombosis of continuous flow ventricular assist devices.

Despite the clinical success and growth in the utilization of continuous flow ventricular assist devices (cfVADs) for the treatment of advanced heart failure, hemolysis and thrombosis remain major limitations. Inadequate and/or ineffective anticoagulation regimens, combined with high pump speed and non-physiological flow patterns, can result in hemolysis which often is accompanied by pump thrombosis. An unexpected increase in cfVADs thrombosis was reported by multiple major VAD implanting centers in 2014, highlighting the association of hemolysis and a rise in lactate dehydrogenase (LDH) presaging thrombotic events. It is well established that thrombotic complications arise from the abnormal shear stresses generated by cfVADs. What remains unknown is the link between cfVAD-associated hemolysis and pump thrombosis. Can hemolysis of red blood cells (RBCs) contribute to platelet aggregation, thereby, facilitating prothrombotic complications in cfVADs? Herein, we examine the effect of RBC-hemolysate and selected major constituents, i.e., lactate dehydrogenase (LDH) and plasma free hemoglobin (pHb) on platelet aggregation, utilizing electrical resistance aggregometry. Our hypothesis is that elements of RBCs, released as a result of shear-mediated hemolysis, will contribute to platelet aggregation. We show that RBC hemolysate and pHb, but not LDH, are direct contributors to platelet aggregation, posing an additional risk mechanism for cfVAD thrombosis.

Specialist by preference, generalist by need: availability of quality hosts drives parasite choice in a natural multihost-parasite system.

Encountering suitable hosts is key for parasite success. A general assumption for disease transmission is that the contact of a parasite with a potential host is driven by the density or relative frequency of hosts. That assumption ignores the potential role of differential host attractiveness for parasites that can drive the encounter of hosts. It has been posited that hosts may be chosen by parasites as a function of their suitability, but the existing literature addressing that hypothesis is still very scarce. In a natural system involving a parasitic Philornis botfly and its multiple bird hosts, there are profound differences in host quality. The Great Kiskadee tolerates and does not invest in resisting the infection, which makes it an optimal host. Alternative hosts are frequently used, but whilst some of them may be good options, others are bad alternatives. Here we examined the host selection processes that drive parasite dynamics in this system with 8 years of data from a longitudinal study under natural conditions. We found that the use of an alternative host was not driven by its density or relative frequency, but instead selection of these hosts was strongly dependent on availability of more suitable hosts. When optimal hosts are plentiful, the parasite tends to ignore alternative ones. As broods of optimal hosts become limited, good alternative hosts are targeted. The parasite chooses bad alternative hosts only when better alternatives are not sufficiently available. These results add evidence from a natural system that some parasites choose their hosts as a function of their profitability, and show that host selection by this parasite is plastic and context-dependent. Such findings could have important implications for the epidemiology of some parasitic and vector-borne infections which should be considered when modelling and managing those diseases. The facultative host selection observed here can be of high relevance for public health, animal husbandry, and biodiversity conservation, because reductions in the richness of hosts might cause humans, domestic animals, or endangered species to become increasingly targeted by parasites that can drive the encounter of hosts.

Contrasting consequences of different defence strategies in a natural multihost-parasite system.

Hosts counteract infections using two distinct defence strategies, resistance (reduction in pathogen fitness) and tolerance (limitation of infection damage). These strategies have been minimally investigated in multi-host systems, where they may vary across host species, entailing consequences both for hosts (virulence) and parasites (transmission). Comprehending the interplay among resistance, tolerance, virulence and parasite success is highly relevant for our understanding of the ecology and evolution of infectious and parasitic diseases. Our work investigated the interaction between an insect parasite and its most common bird host species, focusing on two relevant questions: (i) are defence strategies different between main and alternative hosts and, (ii) what are the consequences (virulence and parasite success) of different defence strategies? We conducted a matched field experiment and longitudinal studies at the host and the parasite levels under natural conditions, using a system comprising Philornis torquans flies and three bird hosts - the main host and two of the most frequently used alternative hosts. We found that main and alternative hosts have contrasting defence strategies, which gave rise in turn to contrasting virulence and parasite success. In the main bird host, minor loss of fitness, no detectable immune response, and high parasite success suggest a strategy of high tolerance and negligible resistance. Alternative hosts, on the contrary, resisted by mounting inflammatory responses, although with very different efficiency, which resulted in highly dissimilar parasite success and virulence. These results show clearly distinct defence strategies between main and alternative hosts in a natural multi-host system. They also highlight the importance of defence strategies in determining virulence and infection dynamics, and hint that defence efficiency is a crucial intervening element in these processes.

Raloxifene modulates interleukin-6 and tumor necrosis factor-alpha synthesis in vivo: results from a pilot clinical study.

Raloxifene (RAL), a selective estrogen receptor modulator, is indicated for the prevention and treatment of postmenopausal osteoporosis. RAL, by decreasing bone turnover, prevents bone loss and microarchitecture damage, reducing the incidence of osteoporotic fractures. Our previous in vitro data demonstrated that RAL modulates osteoclast activity by, at least in part, an IL-6- and TNF-alpha-dependent mechanism. In this study we evaluated the effects of RAL treatment (60 mg/d) on circulating levels of these cytokines in 14 postmenopausal women with osteoporosis. Lumbar bone density (determined by dual energy x-ray absorptiometry) and IL-6 and TNF-alpha levels were measured before and after 6 and 24 months of therapy. After 24 months, RAL increased bone density. IL-6 and TNF-alpha expression, elevated before treatment, significantly decreased (50% and 30%, respectively) after 6 months. This effect was sustained up to the end of the treatment (75% and 35%, respectively). Thus, our data show that RAL can modulate circulating levels of cytokines involved in osteoclastogenesis and bone resorption, suggesting that modulation of soluble factors could play a pivotal role in the mechanisms of the osteoprotective effect of RAL.

Chemotherapy in the elderly with breast cancer.

The number of elderly women diagnosed with breast cancer by 2025, will increase by 72%. These elderly women do not yet participate in most screening programmes. One notes more favourable biological characteristics of the tumour, including more expression of steroid receptors (oestrogen receptor, progesterone receptor), low proliferative rate, good differentiation, normal p53 and low expression of epidermal growth factor. Elderly breast cancer patients are frequently treated with breast conservation, omitting axillary dissection, radiation therapy and chemotherapy. There is a paucity of data to substantiate that such an approach is better than a more radical one. The efficacy of chemotherapy and guidelines for its use vary by tumour stage and patient age. Drugs like modified anthracyclines, vinorelbine, the taxanes and capecitabine may be changing the paradigm of combination therapy superiority.