Adrenomedullin in Ovarian Cancer: Foe In Vitro and Friend In Vivo?

Stromal elements within a tumor interact with cancer cells to create a microenvironment that supports tumor growth and survival. Adrenomedullin (ADM) is an autocrine/paracrine factor produced by both stromal cells and cancer cells to create such a microenvironment. During differentiation of macrophages, ADM is produced in response to pro-inflammatory stimuli and hypoxia. In this study we investigated the role of ADM as a growth factor for ovarian cancer cells and as a modulator of macrophages. We also analyzed ADM expression levels in a retrospective clinical study using nanofluidic technology and assessment of ADM at the gene level in 220 ovarian cancer patients. To study the effects of ADM, ovarian cancer cell lines A2780, OVCAR-3, and HEY and their drug-resistant counterparts were used for proliferation assays, while monocytes from healthy donors were differentiated in vitro. ADM was a weak growth factor, as revealed by proliferation assays and cell cycle analysis. After culturing cancer cells under stressing conditions, such as serum starvation and/or hypoxia, ADM was found to be a survival factor in HEY but not in other cell lines. In macrophages, ADM showed activity on proliferation/differentiation, primarily in type 2 macrophages (M2). Unexpectedly, the clinical study revealed that high expression of ADM was linked to positive outcome and to cancer with low Ca125. In conclusion, although in vitro ADM was a potential factor in biological aggressiveness, this possibility was not confirmed in patients. Therefore, use of an ADM antagonist would be inappropriate in managing ovarian cancer patients.     

Achievement of therapeutic targets in Mexican patients with diabetes mellitus

Background and aimComplications of diabetes comprise the leading cause of death in Mexico. We aimed to describe the characteristics of management and achievement of therapeutic targets in Mexican patients with diabetes mellitus.MethodsWe analyzed data from 2642 Mexican patients with type 1 (T1D, n = 203, 7.7%) and type 2 diabetes (T2D, n = 2439, 92.3%) included in the third wave of the International Diabetes Management Practices Study.ResultsOf T2D patients, 63% were on oral glucose-lowering drugs (OGLD) exclusively (mostly metformin), 11% on insulin, 22% on OGLD plus insulin, and 4% on diet and exercise exclusively. T2D patients on insulin were more likely to be trained on diabetes, but they were older, had worse control, longer disease duration and more chronic complications than patients on OGLD only. Glycated hemoglobin (HbA1c) < 7% was achieved by 21% and 37% of T1D and T2D patients, respectively. Only 5% of T1D and 3% of T2D attained the composite target of HbA1c < 7%, blood pressure < 130/80 mmHg and low-density lipoprotein cholesterol < 100 mg/dl. T1D patients had less macrovascular but more microvascular complications, compared with T2D patients. Late complications increased with disease duration, so that about 80% of patients after 20 years of diagnosis have at least one late complication. Reaching the target HbA1c < 7% was associated with a reduced number of microvascular but not with less macrovascular complications.ConclusionA great proportion of these Mexican patients with diabetes did not reach therapeutic targets. Insulin was used mostly in complicated cases with advanced disease.     

What makes a host profitable? Parasites balance host nutritive resources against immunity

Numerous host qualities can modulate parasite fitness, and among these, host nutritive resources and immunity are of prime importance. Indeed, parasite fitness increases with the amount of nutritive resources extracted from the host body and decreases with host immune response. To maximize fitness, parasites have therefore to balance these two host components. Yet, because host nutritive resources and immunity both increase with host body condition, it is unclear whether parasites perform better on hosts in prime, intermediate, or poor condition. We investigated blood meal size and survival of the ectoparasitic louse fly Crataerina melbae in relation to body condition and cutaneous immune response of their Alpine swift (Apus melba) nestling hosts. Louse flies took a smaller blood meal and lived a shorter period of time when feeding on nestlings that were experimentally food deprived or had their cutaneous immune response boosted with methionine. Consistent with these results, louse fly survival was the highest when feeding on nonexperimental nestlings in intermediate body condition. Our findings emphasize that although hosts in poor condition had a reduced immunocompetence, parasites may have avoided them because individuals in poor condition did not provide adequate resources. These findings highlight the fact that giving host immunocompetence primary consideration can result in a biased appraisal of host-parasite interactions.     

Covariation between egg size and rearing condition determines offspring quality: an experiment with the alpine swift

A positive correlation between egg size, early growth and nestling survival has been frequently reported in the ornithological literature. Albeit of interest, most of these studies did not determine whether the relationship between egg size, early growth and nestling survival was confounded by the quality of rearing conditions. However, this is of importance in order to assess the extent to which a life-history trait like egg size causally affects fitness. In a colony of the alpine swift Apus melba, we cross-fostered complete clutches between nests to determine the relative contribution of egg size and rearing condition on nestling growth and survival. In foster nests, nestlings that hatched out of larger eggs were significantly heavier at birth and at the age of 10 days; at 25 days, however, the relationship was no longer significant. The likelihood of a chick surviving from birth to 25 days of age was not correlated with its original egg size, but with the size of the eggs laid by its foster parents. This experiment therefore lends support to the hypothesis that in the alpine swift the relationship between egg size and nestling growth and survival is mainly due to a covariation between egg size and parental care rather than to a direct contribution of egg size.     

Mental Health Problems in Adolescence and the Interpretation of Unambiguous Threat

Aberrant threat perception has been linked to paranoia, anxiety and other mental health problems, and is widely considered to be a core, transdiagnostic feature of psychopathology. However, to date there has been only limited investigation of whether mental health problems are associated with a biased interpretation of stimuli that have explicit (as opposed to ambiguous) connotations of threat. In the present study, 41 adolescents diagnosed with a mental illness and 45 demographically matched controls were asked to provide danger ratings of stimuli normatively rated as being either low or high in potential threat. All participants were also asked to complete background measures of cognitive function, mental health and wellbeing. The results indicated that the two groups did not differ in their capacity to discriminate between low and high threat stimuli, nor did they differ in the absolute level of threat that they attributed to these stimuli. However, for the control group, the overall level of threat perceived in facial stimuli was correlated with two important indices of mental health (depression and anxiety). No associations emerged in the clinical group. These data are discussed in relation to their potential implications for the role of aberrant threat perception in transdiagnostic models of mental health.     

Phytofiltration of As3+, As5+, and Hg by the aquatic macrophyte Potamogeton pusillus L,and its potential use in the treatment of wastewater

The aim of this paper was to investigate the capacity of the aquatic macrophyte Potamogeton pusillus to remove As³⁺, As⁵⁺, and Hg from aqueous solutions. The plants were exposed to 0 mg.L^?1, 0.1 mg.L^?1, 0.5 mg.L^?1, 1 mg.L^?1, or 2 mg.L^?1 of As³⁺, As⁵⁺, and Hg for 20 days. The results obtained for the individual removal of As³⁺, As⁵⁺, and Hg from water solutions, together with their accumulation in P. pusillus, indicate that this plant can be effectively used for the removal of Hg and of moderate concentrations of As³⁺ or As⁵⁺ (0.1 mg.L^?1) from aquatic systems. Roots and leaves accumulated the highest amount of As when the plant was exposed to As⁵⁺, but when it was exposed to As³⁺, the root accumulated the highest amount of As, and the leaves, the highest amount of Hg. When compared to other aquatic plants species, the results showed that P. pusillus demonstrated a higher Hg accumulation (2465 ± 293 µg.g^?1) when the transfer coefficient was 40,580 ± 3762 L.kg ^?1, showing the great potential of this macrophyte for phytoremediation of water contaminated with Hg. To the extent of our knowledge, this is the first report on bioaccumulation of As³⁺, As⁵⁺, and Hg by P. pusillus.