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1.  The effects of physical activity interventions on glycated haemoglobin A1c in non-diabetic populations: a protocol for a systematic review and meta-analysis 
BMJ Open  2017;7(7):e015801.
Epidemiological evidence suggests that physical activity has a positive effect on reducing glycated haemoglobin A1c (HbA1c) levels not only in diabetics, but also in healthy subjects. Moreover, a positive association of HbA1c levels with cardiovascular disease and mortality in non-diabetic populations has recently been reported. This is a protocol for a systematic review and meta-analysis aiming to estimate the effects of physical activity on glycaemic control measured by HbA1c levels in non-diabetic populations; and to determine which type of physical activity has a greater influence on glycaemic control.
Methods and analysis
The search will be conducted using MEDLINE, EMBASE, the Cochrane Library and Web of Science databases from inception to mid-2017. Randomised controlled trials, non-randomised experimental studies and controlled pre–post studies written in English, Portuguese, French or Spanish will be included. The Cochrane Collaboration’s tool and The Quality Assessment Tool for Quantitative Studies will be used to assess the risk of bias for studies included in the systematic review. Standardised pre–post intervention mean differences of HbA1c will be calculated as the primary outcome. Subgroup analyses will be performed based on the characteristics of physical activity intervention and population included in the studies.
Ethics and dissemination
This systematic review will synthesise evidence on the association of physical activity and HbA1c in non-diabetic populations. This study is important from the clinical and public health point because it will estimate the effect of physical activity on the glycemic control, and it will also examine which is the type of physical activity that should be recommended for preventing type 2 diabetes and its complications. The results will be disseminated by publication in a peer-reviewed journal. Ethical approval will not be required because the data used for this systematic review will be obtained from published studies and there will be no concerns about privacy.
Trial registration number
PROSPERO CRD42016050991.
PMCID: PMC5642781  PMID: 28729317
HbA1c; physical activity; meta-analysis
2.  Moss Mediates the Influence of Shrub Species on Soil Properties and Processes in Alpine Tundra 
PLoS ONE  2016;11(10):e0164143.
In tundra ecosystems, bryophytes influence soil processes directly and indirectly through interactions with overstory shrub species. We experimentally manipulated moss cover and measured seasonal soil properties and processes under two species of deciduous shrubs with contrasting canopy structures, Salix planifolia pulchra and Betula glandulosa-nana complex. Soil properties (seasonal temperature, moisture and C:N ratios) and processes (seasonal litter decomposition and soil respiration) were measured over twelve months. Shrub species identity had the largest influence on summer soil temperatures and soil respiration rates, which were higher under Salix canopies. Mosses were associated with lower soil moisture irrespective of shrub identity, but modulated the effects of shrubs on winter soil temperatures and soil C:N ratios so that moss cover reduced differences in soil winter temperatures between shrub species and reduced C:N ratios under Betula but not under Salix canopies. Our results suggest a central role of mosses in mediating soil properties and processes, with their influence depending on shrub species identity. Such species-dependent effects need to be accounted for when forecasting vegetation dynamics under ongoing environmental changes.
PMCID: PMC5070840  PMID: 27760156
3.  Glycosylated haemoglobin as a predictor of cardiovascular events and mortality: a protocol for a systematic review and meta-analysis 
BMJ Open  2016;6(7):e012229.
Glycosylated haemoglobin level (HbA1c) is an indicator of the average blood glucose concentrations over the preceding 2–3 months and is used as a convenient and well-known biomarker in clinical practice. Currently, epidemiological evidence suggests that HbA1c level is an independent risk factor for cardiovascular events such as myocardial infarction, stroke, coronary heart disease and heart failure. This protocol aim is to conduct a systematic review and meta-analysis to determine relationships of HbA1c levels with cardiovascular outcomes and cause of death, and to analyse the range of HbA1c levels that is a predictor of cardiovascular disease and/or mortality based on data from published observational studies.
Methods and analysis
The search will be conducted using Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science databases from their inception. Observational studies written in Portuguese, Spanish or English will be included. The Quality In Prognosis Studies tool will be used to assess the risk of bias for the studies included in the systematic review or meta-analysis. HRs for cardiovascular outcomes and causes of death with 95% CIs will be determined as primary outcomes. Subgroup analyses will be performed based on cardiovascular outcomes, cause of death studied, and type of population included in the studies.
Ethics and dissemination
This systematic review will synthesise evidence on the potential of using HbA1c level as a prognostic marker for cardiovascular disease outcomes and/or mortality. The results will be disseminated by publication in a peer-reviewed journal. Ethics approval will not be needed because the data used for this systematic review will be obtained from published studies and there will be no concerns about privacy.
Trial registration number
PROSPERO CRD42015032552.
PMCID: PMC4947717  PMID: 27401368
mortality; glycated haemoglobin; cardiovascular disease
4.  Transmissible cytotoxicity of multiple myeloma cells by cord blood-derived NK cells is mediated by vesicle trafficking 
Cell Death and Differentiation  2014;22(1):96-107.
Natural killer cells (NK) are important effectors of anti-tumor immunity, activated either by the downregulation of HLA-I molecules on tumor cells and/or the interaction of NK-activating receptors with ligands that are overexpressed on target cells upon tumor transformation (including NKG2D and NKP30). NK kill target cells by the vesicular delivery of cytolytic molecules such as Granzyme-B and Granulysin activating different cell death pathways, which can be Caspase-3 dependent or Caspase-3 independent. Multiple myeloma (MM) remains an incurable neoplastic plasma-cell disorder. However, we previously reported the encouraging observation that cord blood-derived NK (CB-NK), a new source of NK, showed anti-tumor activity in an in vivo murine model of MM and confirmed a correlation between high levels of NKG2D expression by MM cells and increased efficacy of CB-NK in reducing tumor burden. We aimed to characterize the mechanism of CB-NK-mediated cytotoxicity against MM cells. We show a Caspase-3- and Granzyme-B-independent cell death, and we reveal a mechanism of transmissible cell death between cells, which involves lipid–protein vesicle transfer from CB-NK to MM cells. These vesicles are secondarily transferred from recipient MM cells to neighboring MM cells amplifying the initial CB-NK cytotoxicity achieved. This indirect cytotoxicity involves the transfer of NKG2D and NKP30 and leads to lysosomal cell death and decreased levels of reactive oxygen species in MM cells. These findings suggest a novel and unique mechanism of CB-NK cytotoxicity against MM cells and highlight the importance of lipids and lipid transfer in this process. Further, these data provide a rationale for the development of CB-NK-based cellular therapies in the treatment of MM.
PMCID: PMC4262774  PMID: 25168239
5.  After the frass: foraging pikas select patches previously grazed by caterpillars 
Biology Letters  2013;9(3):20130090.
Interactions among herbivores can shape the structure of their communities and drive their dynamics. However, detecting herbivore interactions can be challenging when they are deferred in space or time. Moreover, interactions among distantly related groups of herbivores, such as vertebrates and invertebrates, are poorly understood. We investigated the effect of invertebrate herbivory on the subsequent foraging choices of a small alpine-dwelling vertebrate, the collared pika (Ochotona collaris). We carried out a field experiment within pika territories, by presenting them with a choice of foraging sites following manipulation of invertebrate (caterpillar) herbivory. Pikas actively selected areas with increased, recent invertebrate herbivory. While the underlying mechanisms behind this interaction remain unknown, our results demonstrate a positive effect of invertebrate herbivores on subsequent vertebrate foraging preferences for the first time. Even among distantly related taxa, such interactions where one herbivore is cueing on the foraging of another, could drive the creation of herbivory hotspots, with cascading consequences for ecosystem processes.
PMCID: PMC3645042  PMID: 23616644
facilitation; grazing succession; herbivory; indirect interactions
6.  The acute effects of strength, endurance and concurrent exercises on the Akt/mTOR/p70S6K1 and AMPK signaling pathway responses in rat skeletal muscle 
The activation of competing intracellular pathways has been proposed to explain the reduced training adaptations after concurrent strength and endurance exercises (CE). The present study investigated the acute effects of CE, strength exercises (SE), and endurance exercises (EE) on phosphorylated/total ratios of selected AMPK and Akt/mTOR/p70S6K1 pathway proteins in rats. Six animals per exercise group were killed immediately (0 h) and 2 h after each exercise mode. In addition, 6 animals in a non-exercised condition (NE) were killed on the same day and under the same conditions. The levels of AMPK, phospho-Thr172AMPK (p-AMPK), Akt, phospho-Ser473Akt (p-Akt), p70S6K1, phospho-Thr389-p70S6K1 (p-p70S6K1), mTOR, phospho-Ser2448mTOR (p-mTOR), and phospho-Thr1462-TSC2 (p-TSC2) expression were evaluated by immunoblotting in total plantaris muscle extracts. The only significant difference detected was an increase (i.e., 87%) in Akt phosphorylated/total ratio in the CE group 2 h after exercise compared to the NE group (P = 0.002). There were no changes in AMPK, TSC2, mTOR, or p70S6K1 ratios when the exercise modes were compared to the NE condition (P ≥ 0.05). In conclusion, our data suggest that low-intensity and low-volume CE might not blunt the training-induced adaptations, since it did not activate competing intracellular pathways in an acute bout of strength and endurance exercises in rat skeletal muscle.
PMCID: PMC3854410  PMID: 23598645
Strength exercise; Concurrent training; Cell signaling; AMPK
7.  Influence of driver nationality on the risk of causing vehicle collisions in Spain 
Study objective: To estimate the association between driver nationality and the risk of causing a collision between vehicles in motion.
Design: Retrospective, matched by collision, case-control study.
Setting: Collisions that occurred in Spain during the period from 1990 to 1999 were studied.
Participants: Responsible (case) and non-responsible (control) drivers identified in the databases of the Dirección General de Tráfico (General Traffic Directorate) who were involved in a collisions between two or more four wheeled vehicles in motion, in which only one of the drivers had committed a traffic violation.
Main results: Crude odds ratios (ORs) for the effect of driver nationality on the risk of causing a collision were significantly higher for foreign drivers than for Spanish drivers, and ranged from a minimum of 1.19 (95% CI 1.09 to 1.29) for Portuguese drivers to a maximum of 2.06 (1.88 to 2.27) for British drivers. Corresponding adjusted ORs were slightly lower, but were still significantly higher than 1 for all nationalities except Italian, Belgian, and American (USA). Adjusted ORs were usually higher for collisions that occurred in urban areas than on open roads.
Conclusions: Authorities responsible for traffic safety, and drivers in general, should consider foreign drivers in Spain at particularly high risk for causing collisions, especially in urban areas.
PMCID: PMC1732138  PMID: 11964439
8.  The MLL recombinome of acute leukemias in 2013 
Leukemia  2013;27(11):2165-2176.
Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (∼90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements.
PMCID: PMC3826032  PMID: 23628958
MLL; chromosomal translocations; translocation partner genes; acute leukemia; ALL; AML

Results 1-8 (8)