Incubation as a driver of maternal effects: Temperature influences levels of yolk maternally derived 5α-dihydrotestosterone.

In birds, maternal hormones deposited into eggs in response to environmental stimuli can impact offspring phenotype. Although less studied, environmental conditions can also influence females' incubation behavior, which might play a role in regulating embryo exposure to maternal hormones through changes in incubation temperature that affect the activity of the enzymes responsible for converting testosterone (T) to 5α-dihydrotestosterone (DHT) or estradiol. Here, we tested the hypothesis that the initial T content of the yolk and incubation temperature determine exposure to T metabolites during early embryo development. In the Japanese quail (Coturnix japonica), we experimentally manipulated yolk T and incubation temperature (38° C versus 36° C) and analyzed DHT and estradiol titers on day four of incubation. We found that eggs with experimentally increased T and those incubated at 36° C showed higher DHT concentration in egg yolk (with no synergistic effect of the two treatments). Estradiol titers were not affected by T manipulation or incubation temperature. Our study suggests that incubation temperature influences DHT titers and may act as an understudied source of maternal influence on offspring phenotype.

Colourful traits in female birds relate to individual condition, reproductive performance and male-mate preferences: a meta-analytic approach.

Colourful traits in females are suggested to have evolved and be maintained by sexual selection. Although several studies have evaluated this idea, support is still equivocal. Evidence has been compiled in reviews, and a handful of quantitative syntheses has explored cumulative support for the link between condition and specific colour traits in males and females. However, understanding the potential function of females' colourful traits in sexual communication has not been the primary focus of any of those previous studies. Here, using a meta-analytic approach, we find that evidence from empirical studies in birds supports the idea that colourful female ornaments are positively associated with residual mass and immune response, clutch size and male-mate preferences. Hence, colourful traits in female birds likely evolved and are maintained by sexual selection as condition-dependent signals.

IGF-1 Levels Increase during an Immune but Not an Oxidative Challenge in an Avian Model, the Japanese Quail.

AbstractInsulin-like growth factor 1 (IGF-1) is positively linked with growth and reproduction but negatively linked with survival, so a potential role of IGF-1 in modulating life history trade-offs has been proposed. However, the underlying mechanisms of the negative link between IGF-1 and survival are not yet clear, and oxidative stress has been proposed as a candidate. Immune activation is one important source of oxidative stress, and both immune activation and oxidative stress are known to reduce survival. We experimentally administrated an immune or oxidative insult to Japanese quails to evaluate whether oxidative stress is a proximate cost of holding elevated IGF-1 levels during a life challenge (e.g., infection, intoxication). IGF-1 levels increased in the presence of the immune insult, but they were not affected by the oxidative insult. Hence, IGF-1 may be linked to the survival costs of activating an immune response, but oxidative stress might not be directly involved as an underlying mechanism.

Both Chloroquine and Lopinavir/Ritonavir Are Ineffective for COVID-19 Treatment and Combined Worsen the Pathology: A Single-Center Experience with Severely Ill Patients.

The off-label use of antiviral and antimalarial drugs has been considered by many researchers as a fast and relatively safe alternative to provide therapeutic options to treat COVID-19, but the assessment of such drug-specific effectiveness in this regard is far from complete. Especially, the current body of knowledge about COVID-19 therapeutics needs more data regarding drug effectiveness and safety in the severely ill patients with comorbidities. In the present article, we retrospectively analyze data from 61 patients that received treatment with chloroquine, lopinavir/ritonavir, both drugs administered together, or a standard treatment with no antiviral drugs, and the study was carried in severely ill patients. We found that either drug is ineffective at treating COVID-19, as they are not able to reduce hospitalization length, mortality, C-reactive protein (CRP), lactate dehydrogenase (LDH), d-Dimer, or ferritin, or to enhance gasometric parameters, lymphocytes, total leukocytes, and neutrophil levels, whereas both drugs administered together decrease circulating lymphocytes, increase LDH and ferritin levels, and more importantly, enhance mortality. In this way, our results show that both drugs are ineffective and even potentially harmful alternatives against SARS-CoV-2.

Tocilizumab reduces COVID-19 mortality and pathology in a dose and timing-dependent fashion: a multi-centric study.

Life-threatening COVID-19 is associated with strong inflammation, where an IL-6-driven cytokine storm appears to be a cornerstone for enhanced pathology. Nonetheless, the specific inhibition of such pathway has shown mixed outcomes. This could be due to variations in the dose of tocilizumab used, the stage in which the drug is administered or the severity of disease presentation. Thus, we performed a retrospective multicentric study in 140 patients with moderate to critical COVID-19, 79 of which received tocilizumab in variable standard doses (< 400 mg, 400-800 mg or > 800 mg), either at the viral (1-7 days post-symptom onset), early inflammatory (8-15) or late inflammatory (16 or more) stages, and compared it with standard treated patients. Mortality, reduced respiratory support requirements and pathology markers were measured. Tocilizumab significantly reduced the respiratory support requirements (OR 2.71, CI 1.37-4.85 at 95%) and inflammatory markers (OR 4.82, CI 1.4-15.8) of all patients, but mortality was only reduced (4.1% vs 25.7%, p = 0.03) when the drug was administered at the early inflammatory stage and in doses ranging 400-800 mg in severely-ill patients. Despite the apparent inability of Tocilizumab to prevent the progression of COVID-19 into a critical presentation, severely-ill patients may be benefited by its use in the early inflammatory stage and moderate doses.

[Permanent consecutive exotropia in children treated with botulinum toxin]. / Exotropía consecutiva permanente en niños tratados con toxina botulínica.

BACKGROUND: Congenital esotropia is the most frequent type of strabismus. Botulinum toxin is a treatment option with variable results. We undertook this study to determine the frequency and associated factors with consecutive permanent esotropia in patients diagnosed with congenital esotropia treated with botulinum toxin. METHODS: A retrospective review was achieved in patients with congenital esotropia treated with botulinum toxin and who remained in esotropia after a minimal follow-up of 6 months. Pre- and postnatal background, cycloplejia, magnitude of the pre-application deviation, injected dose and number of applications were analyzed. RESULTS: A total of 84 patients were included. Of all patients,12 (14.28%) remained in consecutive esotropia (six males and six females). Age range was from 5 months to 2 years (average: 10.75 months). Initial esotropia ranged from 20-50 prism diopters (PD) with an average of 37.9 ± 9.64 PD. One patient had variability in the magnitude of the deviation prior to treatment. During the maximum follow-up, the magnitude of the esotropia was from 10 to 40 (average, SD 18 ± 8.01 PD). In five subjects a variability was observed in the magnitude of the angle of deviation by a range of 10-40 PD, and in seven subjects the deviation was stable with an average of 20 PD. Eleven subjects had some degree of psychomotor delay (91.66%) and one subject had a non-significant history. CONCLUSIONS: In patients with consecutive permanent esotropia after application of botulinum toxin, the most prevalent characteristic is neurological.