The physiology of ventilation

The diffusion of gases brings the partial pressures of O2 and CO2 in blood and alveolar gas to an equilibrium at the pulmonary blood-gas barrier. Alveolar PCO2 (PACO2) dependson the balance between the amount of CO2 being added by pulmonary blood and the amount being eliminated by alveolar ventilation (V\u2d9 A). In steady-state conditions, CO2 output equals CO2 elimination, but during nonsteadystate conditions, phase issues and impaired tissue CO2 clearance make CO2 output less predictable. Lung heterogeneity creates regional differences in CO2 concentration, and sequential emptying raises the alveolar plateau and steepens the expired CO2 slope in expiratory capnograms. Lung areas that are ventilated but not perfused form part of the dead space. Alveolar dead space is potentially large in pulmonary embolism, COPD, and all forms of ARDS. When PEEP recruits collapsed lung units, resulting in improved oxygenation, alveolar dead space may decrease; however, when PEEP induces overdistention, alveolar dead space tends to increase. Measuring physiologic dead space and alveolar ejection volume at admission or examining the trend during mechanical ventilation might provide useful information on outcomes of critically ill patients with ARDS

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

Polyphenols Sensitization Potentiates Susceptibility of MCF-7 and MDA MB-231 Cells to Centchroman

Polyphenols as “sensitizers” together with cytotoxic drugs as “inducers” cooperate to trigger apoptosis in various cancer cells. Hence, their combination having similar mode of mechanism may be a novel approach to enhance the efficacy of inducers. Additionally, this will also enable to achieve the physiological concentrations facilitating significant increase in the activity at concentrations which the compound can individually provide. Here we propose that polyphenols (Resveratrol (RES) and Curcumin (CUR)) pre-treatment may sensitize MCF-7/MDA MB-231 (Human Breast Cancer Cells, HBCCs) to Centchroman (CC, antineoplastic agent). 6 h pre-treated cells with 10 µM RES/CUR and 100 µM RES/30 µM CUR doses, followed by 10 µM CC for 18 h were investigated for Ser-167 ER-phosphorylation, cell cycle arrest, redox homeostasis, stress activated protein kinase (SAPKs: JNK and p38 MAPK) pathways and downstream apoptosis effectors. Low dose RES/CUR enhances the CC action through ROS mediated JNK/p38 as well as mitochondrial pathway in MCF-7 cells. However, RES/CUR sensitization enhanced apoptosis in p53 mutant MDA MB-231 cells without/with involvement of ROS mediated JNK/p38 adjunct to Caspase-9. Contrarily, through high dose sensitization in CC treated cells, the parameters remained unaltered as in polyphenols alone. We conclude that differential sensitization of HBCCs with low dose polyphenol augments apoptotic efficacy of CC. This may offer a novel approach to achieve enhanced action of CC with concomitant reduction of side effects enabling improved management of hormone-dependent breast cancer

Tennis play intensity distribution and relation with aerobic fitness in competitive players

15 p.Los objetivos de este estudio fueron (1) describir la intensidad relativa del juego de tenis simulado en función del tiempo acumulado en tres zonas de intensidad metabólica y (2) determinar las relaciones entre esta distribución de intensidad de juego y la aptitud aeróbica de un grupo de jugadores competitivos. 20 jugadores masculinos de nivel avanzado a élite (ITN) realizaron una prueba de tenis de resistencia específica en el campo incremental hasta el agotamiento para determinar el consumo máximo de oxígeno (VO2max) y los umbrales de ventilación primero y segundo (VT1, VT2). Los parámetros de ventilación y de intercambio de gases se monitorizaron utilizando un analizador de gas portátil telemétrico (K4 b2, Cosmed, Roma, Italia). Dos semanas después, los participantes jugaron un juego de tenis simulado contra un oponente de nivel similar. Las zonas de intensidad (1: baja, 2: moderada y 3: alta) fueron delimitadas por los valores individuales de VO2 correspondientes a VT1 y VT2, y se expresaron como porcentaje del VO2 máximo y la frecuencia cardíaca. Cuando se expresó en relación con el VO 2 máx. El porcentaje de tiempo de juego en la zona 1 (77 ± 25%) fue significativamente mayor (p <0,001) que en la zona 2 (20 ± 21%) y la zona 3 (3 ± 5%). Se encontraron correlaciones positivas de moderadas a altas entre VT1, VT2 y VO2max, y el porcentaje del tiempo de juego transcurrido en la zona 1 (r = 0,68-0,75), así como las correlaciones inversas de bajas a altas entre las variables metabólicas y el porcentaje de tiempo empleado en las zonas 2 y 3 (r = -0.49–0.75). Los jugadores con mejor aptitud aeróbica juegan a intensidades relativamente más bajas. Concluimos que los jugadores pasaron más del 75% del tiempo en su zona de baja intensidad, con menos del 25% del tiempo dedicado a intensidades moderadas a altas. La aptitud aeróbica parece determinar la intensidad metabólica que los jugadores pueden mantener durante todo el juegoS

Potential of Resveratrol Analogues as Antagonists of Osteoclasts and Promoters of Osteoblasts

The plant phytoalexin resveratrol was previously demonstrated to inhibit the differentiation and bone resorbing activity of osteoclasts, to promote the formation of osteoblasts from mesenchymal precursors in cultures, and inhibit myeloma cell proliferation, when used at high concentrations. In the current study, we screened five structurally modified resveratrol analogues for their ability to modify the differentiation of osteoclasts and osteoblasts and proliferation of myeloma cells. Compared to resveratrol, analogues showed an up to 5,000-fold increased potency to inhibit osteoclast differentiation. To a lesser extent, resveratrol analogues also promoted osteoblast maturation. However, they did not antagonize the proliferation of myeloma cells. The potency of the best-performing candidate in vitro was tested in vivo in an ovariectomy-induced model of osteoporosis, but an effect on bone loss could not be detected. Based on their powerful antiresorptive activity in vitro, resveratrol analogues might be attractive modulators of bone remodeling. However, further studies are required to establish their efficacy in vivo

Integrating knowledge exchange and the assessment of dryland management alternatives – A learning-centered participatory approach

The adoption of sustainable land management strategies and practices that respond to current climate and human pressures requires both assessment tools that can lead to better informed decision-making and effective knowledge-exchange mechanisms that facilitate new learning and behavior change. We propose a learning-centered participatory approach that links land management assessment and knowledge exchange and integrates science-based data and stakeholder perspectives on both biophysical and socio-economic attributes. We outline a structured procedure for a transparent assessment of land management alternatives, tailored to dryland management, that is based on (1) principles of constructivism and social learning, (2) the participation of stakeholders throughout the whole assessment process, from design to implementation, and (3) the combination of site-specific indicators, identified by local stakeholders as relevant to their particular objectives and context conditions, and science-based indicators that represent ecosystem services of drylands worldwide. The proposed procedure follows a pattern of eliciting, challenging, and self-reviewing stakeholder perspectives that aims to facilitate learning. The difference between the initial baseline perspectives and the final self-reviewed stakeholder perspectives is used as a proxy of learning. We illustrate the potential of this methodology by its application to the assessment of land uses in a Mediterranean fire-prone area in East Spain. The approach may be applied to a variety of socio-ecological systems and decision-making and governance scales.The PRACTICE protocol was developed in the framework of the project PRACTICE: Prevention and Restoration Actions to Combat Desertification. An integrated Assessment, funded by the European Commission (GA226818). This research was also funded by the European project CASCADE (GA283068), and the Marie Skłodowska-Curie Actions Fellowship of the European Union (GA 629677) “S4S, Science for Society Solutions”, awarded to B.J.O