What is speciation and how should we study it?

To understand speciation, we first need to know what species are. Yet debates over species concepts have seemed endless, with little obvious relevance to the study of speciation. Recently, there has been progress in resolving these debates, favoring a lineage-based, evolutionary species concept. This progress calls for reconsideration of the study of speciation. Traditional speciation research based on the biological species concept has led to great advances in understanding how nonallopatric speciation occurs and how species diverge and remain separate from each other. However, this research has neglected the question of how new species arise in the first place for the most common geographic mode (allopatric). A new and very different research program is needed to understand the ecological and evolutionary processes that split an ancestral species into new allopatric lineages. This research program will connect speciation to many other fundamental questions in evolutionary biology, ecology, biogeography, and conservation biology.     

In vitro activity of the echinocandins. How should it be evaluated?

Echinocandins are a novel class of antifungal drugs. They have good activity against Candida spp and Aspergillus spp. Their low selective toxicity allows their administration at high doses with few secondary side effects. We have reviewed the available data on the endpoints for these drugs in their in vitro susceptibility testing on yeasts and moulds. The microdilution broth method is the most commonly used technique and MIC-1 (80% of growth inhibition) seems to be the most reliable endpoint when yeasts are tested. This endpoint also seems to be the most appropriate for the different drugs when they are combined with echinocandins using the checkerboard method for testing yeasts. By contrast, in the case of moulds, the minimum effective concentration (MEC) correlates better with the in vivo activity than the MIC when echinocandins are tested, and when these drugs are combined with other antifungals, MIC-2 (50% of growth inhibition) seems the most appropriate endpoint. Criteria based on drug pharmacodynamics is the most useful to define the echinocandin endpoints that best correlate with their in vivo efficacy.     

Methotrexate: should it still be considered for chronic calcium pyrophosphate crystal disease?

Chronic calcium pyrophosphate crystal arthritis is a clinical consequence of the formation and deposition of these crystals in joints and can result in persistent arthritis. Curative treatment would require the removal of crystals from joints and tissues, but to date all agents tested have proven ineffective. Management of the inflammatory manifestations of chronic calcium pyrophosphate disease includes glucocorticoids, non-steroidal anti-inflammatory drugs, or colchicine, and responses are usually satisfactory. However, in some patients, the response to these agents is poor or they are contraindicated. Methotrexate had been reported as a promising option in small case series; however, in a recent issue of Arthritis Research & Therapy, a clinical trial failed to confirm the anticipated benefits. Here, we discuss some issues that might have influenced the results of the study, before deciding to abandon methotrexate as a therapeutic option for patients with chronic calcium pyrophosphate arthritis.     

Chronic phase of Chagas disease: why should it be treated? A comprehensive review

The pathogenesis and evolutive pattern of Chagas disease suggests that the chronic phase should be more widely treated in order to (i) eliminate Trypanosoma cruzi and prevent new inflammatory foci and the extension of tissue lesions, (ii) promote tissue regeneration to prevent fibrosis, (iii) reverse existing fibrosis, (iv) prevent cardiomyopathy, megaoesophagus and megacolon and (v) reduce or eliminate cardiac block and arrhythmia. All cases of the indeterminate chronic form of Chagas disease without contraindications due to other concomitant diseases or pregnancy should be treated and not only cases involving children or recently infected cases. Patients with chronic Chagas cardiomyopathy grade II of the New York Heart Association classification should be treated with specific chemotherapy and grade III can be treated according to medical-patient decisions. We are proposing the following new strategies for chemotherapeutic treatment of the chronic phase of Chagas disease: (i) repeated short-term treatments for 30 consecutive days and interval of 30-60 days for six months to one year and (ii) combinations of drugs with different mechanisms of action, such as benznidazole + nifurtimox, benznidazole or nifurtimox + allopurinol or triazole antifungal agents, inhibition of sterol synthesis.     

Oral iron absorption test: should it be performed before starting treatment with ferrous preparations?

Thirty adult male mice were divided into three groups. The animals in group I were used as controls and drank only water during the entire period of experimentation. Group II animals drank water containing 1.5 g/100 mL zinc as ZnSO₄, and group III animals received 2.5 g/100 mL zinc. After 3 wk supplementation with high doses of zinc, the animals were killed and the livers were removed and examined by electron microscopic techniques. After the supplementation period, the animals in groups II and II showed various degrees of degenerative changes in the hepatocytes, such as increased size and the presence of spaces and an abundance of lipid globules in the cytoplasm. The mitochondria showed a crystalline appearance, a diluted matrix, and dense aggregations. Some smooth endoplasmic reticulum tubules showed dilation and were filled with a dense substance. None of these changes were present in the group I control animals.     

The impact of the summer 2003 heat wave in Iberia: how should we measure it?

We present a new approach to improve the reliability of quantifying the impact of a heat wave on mortality rates. We show, for the recent European summer 2003 heat wave, that the use of absolute maximum temperature values, or number of days above a given threshold, can be misleading. Here, we have assessed the impact of the heat wave on Iberian mortality by applying a four step procedure: (1) calculating, for each observatory, the local maximum temperature (T _max) distributions, (2) calculating the corresponding 95th percentile values (T _threshold), (3) locally defining extremely hot days (EHD) as those days on which the local threshold of the 95th percentile of the series is exceeded, and (4) calculating the total degrees-days (DD) of exceedance, by calculating the difference T _max−T _threshold and summing these values for all days above T _threshold. We show that the relationship between summer mortality rates and the DD index is non-linear and can be described by a logarithmic function, with a correlation coefficient of 0.78, which explains 60.6% of the mortality variance (F value of 24.64, significant at P<0.0001). Using maximum temperatures, no significant relationship is found with mortality, whereas the EHD frequency shows a significant association with mortality, albeit weaker than that obtained with DD.