Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism

Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, while the cerebral metabolic rate for oxygen (CMRO2) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, ten male cyclists cycled in the heat for ~2 h with (control) and without fluid replacement (dehydration) while internal (ICA) and external (ECA) carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate the CMRO2. In study 2 (8 males), middle cerebral artery blood velocity (MCA Vmean) was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, ICA flow declined to baseline with progressive dehydration (P < 0.05). However, cerebral metabolism remained stable through enhanced oxygen and glucose extraction (P < 0.05). ECA flow increased for one hour but declined prior to exhaustion. Fluid ingestion maintained cerebral and extra-cranial perfusion throughout non-fatiguing exercise. During exhaustive exercise, however, euhydration delayed but did not prevent the decline in cerebral perfusion. In conclusion, during prolonged exercise in the heat dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extra-cranial perfusion. Thus fatigue is related to reduction in CBF and extra-cranial perfusion rather than in CMRO2.The study was supported by a grant from the Gatorade Sports Science Institute, PepsiCo Inc, USA

Cardiorespiratory and perceptual responses to self-regulated and imposed submaximal arm-leg ergometry

Purpose: This study compared cardiorespiratory and perceptual responses to exercise using self-regulated and imposed power outputs distributed between the arms and legs. Methods Ten males (age 21.7 ± 3.4 years) initially undertook incremental arm-crank ergometry (ACE) and cycle ergometry (CYC) tests to volitional exhaustion to determine peak power output (Wpeak). Two subsequent tests involved 20-min combined arm–leg ergometry (ALE) trials, using imposed and self-regulated protocols, both of which aimed to elicit an exercising heart rate of 160 beats min−1. During the imposed trial, arm and leg intensity were set at 40% of each ergometer-specific Wpeak. During the self-regulated trial, participants were asked to self-regulate cadence and resistance to achieve the target heart rate. Heart rate (HR), oxygen uptake (V˙O2 ), pulmonary ventilation (V˙E ), and ratings of perceived exertion (RPE) were recorded continuously. Results As expected, there were no differences between imposed and self-regulated trials for HR, V˙O2 , and V˙E (all P ≥ 0.05). However, central RPE and local RPE for the arms were lower during self-regulated compared imposed trials (P ≤ 0.05). Lower RPE during the self-regulated trial was related to preferential adjustments in how the arms (33 ± 5% Wpeak) and legs (46 ± 5% Wpeak) contributed to the exercise intensity. Conclusions: This study demonstrates that despite similar metabolic and cardiovascular strain elicited by imposed and self-regulated ALE, the latter was perceived to be less strenuous, which is related to participants doing more work with the legs and less work with the arms to achieve the target intensity

Temporal variability of contaminated sediments in a strongly regulated reservoir of the upper Rhine River

Water Qualit

Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention

Evaluation of Specific Symptoms of Bacterial Vaginosis Among Pregnant Women

Objective: Identification of the symptoms of bacterial vaginosis (BV) in pregnancy might be rational in order to identify a possible BV-associated group at risk of preterm delivery

Application of real-time global media monitoring and ‘derived questions’ for enhancing communication by regulatory bodies:the case of human papillomavirus vaccines

Abstract Background The benefit-risk balance of vaccines is regularly debated by the public, but the utility of media monitoring for regulatory bodies is unclear. A media monitoring study was conducted at the European Medicines Agency (EMA) concerning human papillomavirus (HPV) vaccines during a European Union (EU) referral procedure assessing the potential causality of complex regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome (POTS) reported to the authorities as suspected adverse reactions. Methods To evaluate the utility of media monitoring in real life, prospective real-time monitoring of worldwide online news was conducted from September to December 2015 with inductive content analysis, generating ‘derived questions’. The evaluation was performed through the validation of the predictive capacity of these questions against journalists’ queries, review of the EMA’s public statement and feedback from EU regulators. Results A total of 4230 news items were identified, containing personal stories, scientific and policy/process-related topics. Explicit and implicit concerns were identified, including those raised due to lack of knowledge or anticipated once more information would be published. Fifty derived questions were generated and categorised into 12 themes. The evaluation demonstrated that providing the media monitoring findings to assessors and communicators resulted in (1) confirming that public concerns regarding CRPS and POTS would be covered by the assessment; (2) meeting specific information needs proactively in the public statement; (3) predicting all queries from journalists; and (4) altering the tone of the public statement with respectful acknowledgement of the health status of patients with CRSP or POTS. Conclusions The study demonstrated the potential utility of media monitoring for regulatory bodies to support communication proactivity and preparedness, intended to support trusted safe and effective vaccine use. Derived questions seem to be a familiar and effective format for presenting media monitoring results in the scientific-regulatory environment. It is suggested that media monitoring could form part of regular surveillance for medicines of high public interest. Future work is recommended to develop efficient monitoring strategies for that purpose

Application of real-time global media monitoring and ‘derived questions’ for enhancing communication by regulatory bodies:the case of human papillomavirus vaccines

Abstract Background The benefit-risk balance of vaccines is regularly debated by the public, but the utility of media monitoring for regulatory bodies is unclear. A media monitoring study was conducted at the European Medicines Agency (EMA) concerning human papillomavirus (HPV) vaccines during a European Union (EU) referral procedure assessing the potential causality of complex regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome (POTS) reported to the authorities as suspected adverse reactions. Methods To evaluate the utility of media monitoring in real life, prospective real-time monitoring of worldwide online news was conducted from September to December 2015 with inductive content analysis, generating ‘derived questions’. The evaluation was performed through the validation of the predictive capacity of these questions against journalists’ queries, review of the EMA’s public statement and feedback from EU regulators. Results A total of 4230 news items were identified, containing personal stories, scientific and policy/process-related topics. Explicit and implicit concerns were identified, including those raised due to lack of knowledge or anticipated once more information would be published. Fifty derived questions were generated and categorised into 12 themes. The evaluation demonstrated that providing the media monitoring findings to assessors and communicators resulted in (1) confirming that public concerns regarding CRPS and POTS would be covered by the assessment; (2) meeting specific information needs proactively in the public statement; (3) predicting all queries from journalists; and (4) altering the tone of the public statement with respectful acknowledgement of the health status of patients with CRSP or POTS. Conclusions The study demonstrated the potential utility of media monitoring for regulatory bodies to support communication proactivity and preparedness, intended to support trusted safe and effective vaccine use. Derived questions seem to be a familiar and effective format for presenting media monitoring results in the scientific-regulatory environment. It is suggested that media monitoring could form part of regular surveillance for medicines of high public interest. Future work is recommended to develop efficient monitoring strategies for that purpose

Early holocenic and historic mtDNA african signatures in the iberian peninsula: The andalusian region as a paradigm

Determining the timing, identity and direction of migrations in the Mediterranean Basin, the role of "migratory routes" in and among regions of Africa, Europe and Asia, and the effects of sex-specific behaviors of population movements have important implications for our understanding of the present human genetic diversity. A crucial component of the Mediterranean world is its westernmost region. Clear features of transcontinental ancient contacts between North African and Iberian populations surrounding the maritime region of Gibraltar Strait have been identified from archeological data. The attempt to discern origin and dates of migration between close geographically related regions has been a challenge in the field of uniparental-based population genetics. Mitochondrial DNA (mtDNA) studies have been focused on surveying the H1, H3 and V lineages when trying to ascertain north-south migrations, and U6 and L in the opposite direction, assuming that those lineages are good proxies for the ancestry of each side of the Mediterranean. To this end, in the present work we have screened entire mtDNA sequences belonging to U6, M1 and L haplogroups in Andalusians--from Huelva and Granada provinces--and Moroccan Berbers. We present here pioneer data and interpretations on the role of NW Africa and the Iberian Peninsula regarding the time of origin, number of founders and expansion directions of these specific markers. The estimated entrance of the North African U6 lineages into Iberia at 10 ky correlates well with other L African clades, indicating that U6 and some L lineages moved together from Africa to Iberia in the Early Holocene. Still, founder analysis highlights that the high sharing of lineages between North Africa and Iberia results from a complex process continued through time, impairing simplistic interpretations. In particular, our work supports the existence of an ancient, frequently denied, bridge connecting the Maghreb and Andalusia.Financial support was provided by the Spanish Ministry of Competitiveness through Research Project CGL2010-15191/BOS granted to RC and International Mobility Program Acciones Integradas Hispano-Portuguesas (PRI-AIBPT-2011-1004) granted to RC (Spain) and LP (Portugal) (http://www.mineco.gob.es/portal/site/mineco/idi). The E.C. Sixth Framework Programme under Contract n° ERAS-CT-2003-980409 (EUROCORES project of the European Science Foundation) also provided financial support to JMD for North African population research. CLH has a predoctoral fellowship granted by Complutense University. PS is supported by FCT Investigator Programme (IF/01641/2013). IPATIMUP (https://www.ipatimup.pt/) integrates the Instituto the Investigação em Saúde (i3S) Research Unit, which is partially supported by FCT, the Portuguese Foundation for Science and Technology. IPATIMUP is funded by FEDER funds through the Operational Programme for Competitiveness Factors - COMPETE and National Funds through the FCT - under the project PEst-C/SAU/LA0003/2013. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

CC9 Livestock-Associated Staphylococcus aureus Emerges in Bloodstream Infections in French Patients Unconnected With Animal Farming

We report 4 bloodstream infections associated with CC9 agr type II Staphylococcus aureus in individuals without animal exposure. We demonstrate, by microarray analysis, the presence of egc cluster, fnbA, cap operon, lukS, set2, set12, splE, splD, sak, epiD, and can, genomic features associated with a high virulence potential in human