Latitudinal but not elevational variation in blood glucose level is linked to life history across passerine birds.

Macrophysiological research is vital to our understanding of mechanisms underpinning global life history variation and adaptation to diverse environments. Here, we examined latitudinal and elevational variation in a key substrate of energy metabolism and an emerging physiological component of pace-of-life syndromes, blood glucose concentration. Our data, collected from 61 European temperate and 99 Afrotropical passerine species, revealed that baseline blood glucose increases with both latitude and elevation, whereas blood glucose stress response shows divergent directions, being stronger at low latitudes and high elevations. Low baseline glucose in tropical birds, compared to their temperate counterparts, was mainly explained by their low fecundity, consistent with the slow pace-of-life syndrome in the tropics. In contrast, elevational variation in this trait was decoupled from fecundity, implying a unique montane pace-of-life syndrome combining slow-paced life histories with fast-paced physiology. The observed patterns suggest that pace-of-life syndromes do not evolve along the single fast-slow axis.

Feather growth and quality across passerines is explained by breeding rather than moulting latitude.

Tropical bird species are characterized by a comparatively slow pace of life, being predictably different from their temperate zone counterparts in their investments in growth, survival and reproduction. In birds, the development of functional plumage is often considered energetically demanding investment, with consequences on individual fitness and survival. However, current knowledge of interspecific variation in feather growth patterns is mostly based on species of the northern temperate zone. We evaluated patterns in tail feather growth rates (FGR) and feather quality (stress-induced fault bar occurrence; FBO), using 1518 individuals of 167 species and 39 passerine families inhabiting Afrotropical and northern temperate zones. We detected a clear difference in feather traits between species breeding in the temperate and tropical zones, with the latter having significantly slower FGR and three times higher FBO. Moreover, trans-Saharan latitudinal migrants resembled temperate zone residents in that they exhibited a comparatively fast FGR and low FBO, despite sharing moulting environments with tropical species. Our results reveal convergent latitudinal shifts in feather growth investments (latitudinal syndrome) across unrelated passerine families and underscore the importance of breeding latitude in determining cross-species variation in key avian life-history traits.

Codiversification of gastrointestinal microbiota and phylogeny in passerines is not explained by ecological divergence.

Vertebrate gut microbiota (GM) is comprised of a taxonomically diverse consortium of symbiotic and commensal microorganisms that have a pronounced effect on host physiology, immune system function and health status. Despite much research on interactions between hosts and their GM, the factors affecting inter- and intraspecific GM variation in wild populations are still poorly known. We analysed data on faecal microbiota composition in 51 passerine species (319 individuals) using Illumina MiSeq sequencing of bacterial 16S rRNA (V3-V4 variable region). Despite pronounced interindividual variation, GM composition exhibited significant differences at the interspecific level, accounting for approximately 20%-30% of total GM variation. We also observed a significant correlation between GM composition divergence and host's phylogenetic divergence, with strength of correlation higher than that of GM vs. ecological or life history traits and geographic variation. The effect of host's phylogeny on GM composition was significant, even after statistical control for these confounding factors. Hence, our data do not support codiversification of GM and passerine phylogeny solely as a by-product of their ecological divergence. Furthermore, our findings do not support that GM vs. host's phylogeny codiversification is driven primarily through trans-generational GM transfer as the GM vs. phylogeny correlation does not increase with higher sequence similarity used when delimiting operational taxonomic units. Instead, we hypothesize that the GM vs. phylogeny correlation may arise as a consequence of interspecific divergence of genes that directly or indirectly modulate composition of GM.

Stereotactic Body Radiotherapy of Lymph Node Oligometastases.

BACKGROUND: The aim of this retrospective study is to evaluate the efficacy and toxicity of extracranial stereotactic radiotherapy for the treatment of oligometastatic lymph node involvement in the mediastinum, retroperitoneum, and pelvis in a consecutive group of patients from real clinical practice. MATERIAL AND METHODS: Of a total of 50 patients treated between 2011 and 2017, 29 were men and 21 were women, and the mean age was 62 years (median 66 years, range 25-81 years). Patients were most often irradiated in five fractions; the dose was selected according to dose-volume histograms of organs-at-risk in proximity to the planning target volume. The primary objectives were local control (LC), progression-free survival (PFS), time to multiple dissemination not allowing the use of local treatment methods (freedom from widepread dissemination - FFWD), and overall survival (OS). Acute and delayed toxicity were evaluated as well. RESULTS: The median dose equivalent at α/β = 10 (BED10) was 54 Gy (range 48-80 Gy). The median follow-up period was 40.4 months. LC after irradiation was 90% in 1 year and 75% in 3 years. Median time to local progression was not achieved. Patients irradiated with a high dose had significantly better LC than patients irradiated with a low dose; the cut-off was the median of the applied dose (ie BED10 = 54 Gy). Pathological node localization had no significant effect on LC. The median PFS was 8.2 months (95% CI 7.4-11.6 months). PFS in 1 year was 38.5% and 17% in 3 years. The median OS was 37.3 months (95% CI 23.2-51.4 months). One-year OS was 83% and 3-year OS was 51%. The median FFWD was 13.6 months (range 8.7-18.5 months). The one-year FFWD was 55% and the 3-year FFWD was 24%. None of these parameters (PFS, OS, FFWD) was dose or localization dependent. No grade III or IV toxicity was reported. CONCLUSION: Our study shows that targeted stereotactic radiotherapy is a very effective low toxic treatment for oligometastatic lymph node involvement. It can delay cytotoxic chemotherapy and thus improve/maintain the quality of life of patients. Approximately one fifth of patients treated with extracranial stereotactic radiotherapy for oligometastatic lymph node involvement survived without signs of disease for prolonged periods. Future studies should aim at identifying patients who would benefit most from this treatment, adjusting the timing of extracranial stereotactic radiotherapy depending on the treatment strategy, and optimizing the dose prescription. This work was supported by grant of the Ministry of Health of the Czech Republic AZV 19-00354 and by grant of the Ministry of Health of the Czech Republic - Conceptual development of a research organization (MMCI 00209805). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Stereotactic Body Radiotherapy for Lymph Node Oligometastases: Real-World Evidence From 90 Consecutive Patients.

AIMS: To evaluate the efficacy and toxicity of extracranial stereotactic body radiotherapy (SBRT) in the treatment of oligometastatic lymph node involvement in the mediastinum, retroperitoneum, or pelvis, in a consecutive group of patients from real clinical practice outside clinical trials. METHODS: A retrospective analysis of 90 patients with a maximum of four oligometastases and various primary tumors (the most common being colorectal cancers). The endpoints were local control of treated metastases (LC), freedom from widespread dissemination (FFWD), progression-free survival (PFS), overall survival (OS), and freedom from systemic treatment (FFST). Acute and delayed toxicities were also evaluated. RESULTS: The median follow-up after SBRT was 34.9 months. The LC rate at three and five years was 68.4 and 56.3%, respectively. The observed median FFWD was 14.6 months, with a five-year FFWD rate of 33.7%. The median PFS was 9.4 months; the three-year PFS rate was 19.8%. The median FFST was 14.0 months; the five-year FFST rate was 23.5%. The OS rate at three and five years was 61.8 and 39.3%, respectively. Median OS was 53.1 months. The initial dissemination significantly shortened the time to relapse, death, or activation of systemic treatment-LC (HR 4.8, p < 0.001), FFWD (HR 2.8, p = 0.001), PFS (HR 2.1, p = 0.011), FFST (HR 2.4, p = 0.005), OS (HR 2.2, p = 0.034). Patients classified as having radioresistant tumors noticed significantly higher risk in terms of LC (HR 13.8, p = 0.010), FFWD (HR 3.1, p = 0.006), PFS (HR 3.5, p < 0.001), FFST (HR 3.2, p = 0.003). The multivariable analysis detected statistically significantly worse survival outcomes for initially disseminated patients as well as separately in groups divided according to radiosensitivity. No grade III or IV toxicity was reported. CONCLUSION: Our study shows that targeted SBRT is a very effective and low toxic treatment for oligometastatic lymph node involvement. It can delay the indication of cytotoxic chemotherapy and thus improve and maintain patient quality of life. The aim of further studies should focus on identifying patients who benefit most from SBRT, as well as the correct timing and dosage of SBRT in treatment strategy.

Early toxicity of hypofractionated radiotherapy for prostate cancer.

BACKGROUND: Hypofractionated accelerated radiotherapy (HART) is now a feasible option for prostate cancer treatment apropos toxicity, biochemical control and shortening of treatment. The aim of this study was to investigate hypofractionated schedules in the treatment of patients with localized prostate cancer. PATIENTS AND METHODS: Between 2011-2014, 158 patients were treated using the RapidArc technique with IGRT. The target volume for low risk patients was the prostate alone with a prescribed dose of 20x3.0 Gy (EQD2=77 Gy). Targets volumes for intermediate and high risk patients were prostate and two thirds of the seminal vesicles with a prescribed dose 21-22x3.0/2.1 Gy (EQD2=81/45.4-84.9/47.5). Based on radiobiological modelling of early toxicity, we used four fractions per week in the low risk group and four fractions in odd weeks and three fractions in even weeks in intermediate and high risk groups. The RTOG/EORTC toxicity scale was used. RESULTS: Early genitourinary (GU) toxicity was observed for grades 0, 1, 2, 3 and 4 in 73 (46%), 60 (38%), 22 (14%), 0 and 3 (2%), respectively; early gastrointestinal (GI) toxicity was recorded for grades 0, 1, 2 and 3 in 119 (75%), 37 (23%), and 2 (1%) patients, respectively. CONCLUSION: A combination of moderate hypofractionation, number of fractions per week adapted to target volume and precise dose delivery technique with image guidance appears safe with low early toxicity. Longer follow up is needed to assess late toxicity and tumor control probability.