Effects of chainring design on performance in competitive cyclists

The development of noncircular chainrings to improve cycling performance has been in progress since the 1980’s and continues apace. The aim of this study was to compare performance time and physiological responses in cycling using a standard circular chainring versus a noncircular chainring developed in 2005: the Rotor Q-Ring. Eight competitive male cyclists were pre-tested using the original circular chainrings and also on the initial week of testing. The intervention consisted of cycling with Rotor Q-Rings for four weeks. Post-testing occurred with the original chainrings for the final week of testing. Testing consisted of a maximal or submaximal graded exercise test followed by a 1 k time trial. Oxygen consumption, carbon dioxide output, heart rate, ventilation, respiratory exchange ratio, and perceived exertion were continuously measured during the tests. Blood lactate concentration was measured during the last 30 s of each three minute stage. Five minutes after the submaximal test, participants performed an “all out” 1 k trial for time as well as maximum and average power. The main findings were: 1) Participants were on average 1.6 seconds faster in the 1 k time trial with Rotor Q-Rings compared to a circular chainrings. 2) There was a significant increase in average power (26.7 watts) and average speed (0.7 kph) during the 1 k time trial with Rotor Q-Rings. 3) Oxygen consumption (during weeks 2-4) and heart rate (weeks 1-3) were significantly lower with Rotor Q-Rings during submaximal testing when compared to circular chainrings. However, in contrast to our hypotheses no benefits were observed for other submaximal dependent measures (i.e., CO2, VE, RER, RPE, GE, DE, and lactate)

Human RELMβ is a mitogenic factor in lung cells and induced in hypoxia

AbstractRELMβ (resistin-like molecule) represents the most related human homologue of mouse RELMα, also known as hypoxic-induced mitogenic factor (HIMF). In this study, we isolated RELMβ cDNA from human lung tissue and performed regulatory and functional expression studies. RELMβ mRNA was upregulated in hypoxia in human lung A549 cell line as well as primary cultured adventitial fibroblasts and smooth muscle cells (SMC) of pulmonary arteries. Upon transfection of a RELMβ encoding expression plasmid into these cells, we observed significant induction of proliferation particularly in SMC and A549 cells, which could be blocked by phosphatidyl-inositol 3-kinase (PI3K) inhibitors LY294002 and wortmannin. The results suggest that human RELMβ may contribute to hypoxic-induced pulmonary vascular remodeling processes or hypoxia related fibrotic lung disease

Secreted Amyloid Precursor Protein β and Secreted Amyloid Precursor Protein α Induce Axon Outgrowth In Vitro through Egr1 Signaling Pathway

BACKGROUND: sAPPα released after α secretase cleavage of Amyloid Precursor Protein (APP) has several functions including the stimulation of neurite outgrowth although detailed morphometric analysis has not been done. Two domains involved in this function have been described and are present in sAPPβ released at the first step of amyloid peptide cleavage, raising the possibility that sAPPβ could also stimulate neurite outgrowth. We investigated the morphological effects of sAPPα and sAPPβ on primary neurons and identified a key signaling event required for the changes observed. METHODOLOGY/PRINCIPAL FINDINGS: Final concentrations of 50 to 150 nM bacterial recombinant sAPPα or sAPPβ added to primary neuronal cultures after 1 day in vitro decreased cell adhesion 24 hours later and primary dendrite length 96 hours later. 150 nM sAPPα and sAPPβ induced a similar increase of axon outgrowth, although this increase was already significant at 100 nM sAPPα. These morphological changes induced by sAPPs were also observed when added to differentiated neurons at 5 days in vitro. Real time PCR and immunocytochemistry showed that sAPPα and sAPPβ stimulated Egr1 expression downstream of MAPK/ERK activation. Furthermore, in primary neurons from Egr1 -/- mice, sAPPs affected dendritic length but did not induce any increase of axon length. CONCLUSION/SIGNIFICANCE: sAPPα and sAPPβ decrease cell adhesion and increase axon elongation. These morphological changes are similar to what has been observed in response to heparan sulfate. The sAPPα/sAPPβ stimulated increase in axon growth requires Egr1 signaling. These data suggest that sAPPβ is not deleterious per se. Since sAPPβ and sAPPα are present in the embryonic brain, these two APP metabolites might play a role in axon outgrowth during development and in response to brain damage

Cyclotraxin-B, the First Highly Potent and Selective TrkB Inhibitor, Has Anxiolytic Properties in Mice

In the last decades, few mechanistically novel therapeutic agents have been developed to treat mental and neurodegenerative disorders. Numerous studies suggest that targeting BDNF and its TrkB receptor could be a promising therapeutic strategy for the treatment of brain disorders. However, the development of potent small ligands for the TrkB receptor has proven to be difficult. By using a peptidomimetic approach, we developed a highly potent and selective TrkB inhibitor, cyclotraxin-B, capable of altering TrkB-dependent molecular and physiological processes such as synaptic plasticity, neuronal differentiation and BDNF-induced neurotoxicity. Cyclotraxin-B allosterically alters the conformation of TrkB, which leads to the inhibition of both BDNF-dependent and -independent (basal) activities. Finally, systemic administration of cyclotraxin-B to mice results in TrkB inhibition in the brain with specific anxiolytic-like behavioral effects and no antidepressant-like activity. This study demonstrates that cyclotraxin-B might not only be a powerful tool to investigate the role of BDNF and TrkB in physiology and pathology, but also represents a lead compound for the development of new therapeutic strategies to treat brain disorders

‘Bonkers but good!’ – Using illustration-based interview methods to understand land management and conservation visions

Visions help to understand common ground and tensions among citizens and stakeholders, supporting inclusive land management and conservation solutions to the climate emergency and biodiversity crisis. With careful design and sufficient resource, it is possible to bring together communities and other stakeholders to share perspectives and deliberate desired futures, identifying more acceptable alternatives and avoiding costly delays. We evaluated researcher and participant experiences of illustration-based interviews to understand land management visions using four studies in Scotland, The Netherlands and Spain. These studies used STREAMLINE, a visual mixed-method interview format using thematic illustrated canvases designed to provide an inclusive and creative framing for participants to contemplate their desired future. Participants enjoyed the informal visual format, which reduced pressure, increased comfort through the research process, and helped their thinking and reflection about complex topics. They also valued being listened to and having the opportunity to share their views. Researchers appreciated the ability to triangulate rich qualitative data with a variety of quantitative measure through the mixed-method format and the flexibility to adapt the canvases to suit their research aims. Positive participant experience made facilitation easier and was stimulating for the researchers. The credibility and legitimacy of illustration-based interviews will ultimately depend on specific research design-decisions and testing, which can make the approach more resource intensive than conventional interviews. While organisational barriers should be considered realistically, illustration-based interviews can have high saliency by providing useful and usable insights that strengthen land management policy and planning

‘Bonkers but good!’ – Using illustration-based interview methods to understand land management and conservation visions

Forest biodiversity studies conduct Visions help to understand common ground and tensions among citizens and stakeholders, supporting inclusive land management and conservation solutions to the climate emergency and biodiversity crisis. With careful design and sufficient resource, it is possible to bring together communities and other stakeholders to share perspectives and deliberate desired futures, identifying more acceptable alternatives and avoiding costly delays. We evaluated researcher and participant experiences of illustration-based interviews to understand land management visions using four studies in Scotland, The Netherlands and Spain. These studies used STREAMLINE, a visual mixed-method interview format using thematic illustrated canvases designed to provide an inclusive and creative framing for participants to contemplate their desired future. Participants enjoyed the informal visual format, which reduced pressure, increased comfort through the research process, and helped their thinking and reflection about complex topics. They also valued being listened to and having the opportunity to share their views. Researchers appreciated the ability to triangulate rich qualitative data with a variety of quantitative measure through the mixed-method format and the flexibility to adapt the canvases to suit their research aims. Positive participant experience made facilitation easier and was stimulating for the researchers. The credibility and legitimacy of illustration-based interviews will ultimately depend on specific research design-decisions and testing, which can make the approach more resource intensive than conventional interviews. While organisal barriers should be considered realistically, illustration-based interviews can have high saliency by providing useful and usable insights that strengthen land management policy and planning. Inclusive Conservation Participatory planning Governance Visions Visual methods Participatory methods d across Europe use a multitude of forestry terms, often inconsistently. This hinders the comparability across studies and makes the assessment of the impacts of forest management on biodiversity highly context-dependent. Recent attempts to standardize forestry and stand description terminology mostly used a top-down approach that did not account for the perspectives and approaches of forest biodiversity experts. This work aims to establish common standards for silvicultural and vegetation definitions, creating a shared conceptual framework for a consistent study on the effects of forest management on biodiversity. We have identified both strengths and weaknesses of the silvicultural and vegetation information provided in forest biodiversity studies. While quantitative data on forest biomass and dominant tree species are frequently included, information on silvicultural activities and vegetation composition is often lacking, shallow, or based on broad and heterogeneous classifications. We discuss the existing classifications and their use in European forest biodiversity studies through a novel bottom-up and top-driven review process, and ultimately propose a common framework. This will enhance the comparability of forest biodiversity studies in Europe, and puts the basis for effective implementation and monitoring of sustainable forest management policies. The standards here proposed are potentially adaptable and applicable to other geographical areas and could be extended to other forest interventions.publishedVersio

Genital ulcers in women: clinical, microbiologic and histopathologic characteristics

Female genital ulcer is a disease that affects a large number of women, and its etiologic diagnosis can be difficult. The disease may increase the risk of acquiring HIV. Genital ulcer may be present in sexually transmitted diseases (STD) - syphilis, chancroid, genital herpes, donovanosis, lymphogranuloma venereum and other non-STD disorders (NSTD) - Behçet's syndrome, pemphigus, Crohn's disease, erosive lichen planus and others. This study evaluated the clinical-histopathologic-microbiologic characteristics of female genital ulcers. A cross-sectional descriptive prospective study was conducted during a six-month period to investigate the first 53 women without a definitive diagnosis, seeking medical care for genital ulcers at a genital infections outpatient facility in a university hospital. A detailed and specific history was taken, followed by a dermatologic and gynecologic examination. In addition to collecting material from the lesions for microbiologic study, a biopsy of the ulcer was performed for histopathologic investigation. The average age of the patients was 32.7 years, 56.6% had junior high school education and higher education. The most frequent etiology was herpetic lesion, followed by auto-immune ulcers. At the time of their first consultation, around 60% of the women were using inadequate medication that was inconsistent with the final diagnosis. Histologic diagnosis was conclusive in only 26.4% of the patients (14/53). Cure was obtained in 99% of the cases after proper therapy. The female genital ulcers studied were equally distributed between sexually transmitted and non-sexually transmitted causes. Herpes was the most frequent type of genital ulcer, affecting women indiscriminately, mostly between the ages of 20 and 40 years. The etiologic diagnosis of herpetic ulcers is difficult to make even when various diagnostic methods are applied. It is imperative that NSTD should be included in the differential diagnoses of female genital ulcers. The histopathologic exam is not a diagnostic tool in the majority of cases and should not be considered the gold standard test, being of little value in cases of NSTD and STD ulcers.25426

Trajectories of Health-Related Quality of Life and HbA1c Values of Children and Adolescents With Diabetes Mellitus Type 1 Over 6 Months: A Longitudinal Observational Study

Introduction: To achieve optimized blood glucose concentrations (assessed by HbA1c) and high health-related quality of life (HRQL), children and adolescents with diabetes mellitus type 1 (T1DM) must follow strict disease management strategies. This study aims to investigate HRQL of children and adolescents with T1DM and its association with HbA1c values over the course of 6 months. Methods: Patients aged 7-17 years (n = 203) with T1DM provided HRQL data on a monthly basis. HRQL was measured using the Kids-CAT, a computer-adaptive test (CAT) comprising five generic HRQL domains. HbA1c concentrations were assessed at baseline, at 3 and 6 months. We explored the trajectory of HRQL at the domain level using linear mixed effects models. Further, we investigated the association between HRQL and HbA1c concentrations over time using path analysis models. Results: Children and adolescents with T1DM reported high scores across all HRQL domains over time. However, those with an HbA1c concentrations of \u3e 9.0% reported significantly lower scores in physical well-being and parent relations compared with those with an HbA1c concentration of \u3c 7.5%. Path analysis models revealed a minimal temporal relationship between HbA1c and HRQL, with a small negative impact of HbA1c on physical well-being, psychological well-being and parent relations. Conclusion: Although observed HRQL of young patients with T1DM was comparable to age-related German-speaking reference population over the course of 6 months, those with an HbA1c concentration \u3e 9.0% reported lower scores in selected HRQL domains. Thus, special attention should be drawn to HRQL of children and adolescents with higher HbA1c concentrations. The minimal relationship between HbA1c and HRQL indicates that the two therapy goals, i.e., achievement and maintenance of glycemic targets and high HRQL, should be considered and evaluated independently in clinical routine. Trial Registration: DRKS00006326 (German Clinical Trial Register), date of registration: August 1st, 2014

Regulated mitochondrial DNA replication during oocyte maturation is essential for successful porcine embryonic development.

Cellular ATP is mainly generated through mitochondrial oxidative phosphorylation, which is dependent on mitochondrial DNA (mtDNA). We have previously demonstrated the importance of oocyte mtDNA for porcine and human fertilization. However, the role of nuclear-encoded mitochondrial replication factors during oocyte and embryo development is not yet understood. We have analyzed two key factors, mitochondrial transcription factor A (TFAM) and polymerase gamma (POLG), to determine their role in oocyte and early embryo development. Competent and incompetent oocytes, as determined by brilliant cresyl blue (BCB) dye, were assessed intermittently during the maturation process for TFAM and POLG mRNA using real-time RT-PCR, for TFAM and POLG protein using immunocytochemistry, and for mtDNA copy number using real-time PCR. Analysis was also carried out following treatment of maturing oocytes with the mtDNA replication inhibitor, 2',3'-dideoxycytidine (ddC). Following in vitro fertilization, preimplantation embryos were also analyzed. Despite increased levels of TFAM and POLG mRNA and protein at the four-cell stage, no increase in mtDNA copy number was observed in early preimplantation development. To compensate for this, mtDNA appeared to be replicated during oocyte maturation. However, significant differences in nuclear-encoded regulatory protein expression were observed between BCB(+) and BCB(-) oocytes and between untreated oocytes and those treated with ddC. These changes resulted in delayed mtDNA replication, which correlated to reduced fertilization and embryonic development. We therefore conclude that adherence to the regulation of the timing of mtDNA replication during oocyte maturation is essential for successful embryonic development

Risks for human and animal health related to the presence of phorbol esters in Jatropha kernel meal

The Panel wishes to thank the members of the Working Group on Phorbol Esters: Bruce Cottrill, Stefano Dall'Acqua, Johanna Fink-Gremmels, Harinder P.S. Makkar and Manfred Metzler for the preparatory work on this scientific opinion, and EFSA staff: Marco Binaglia, Karen Mackay and Rositsa Serafimova for the support provided to this scientific opinion.Peer reviewedPublisher PD