Ticagrelor Reduces Thromboinflammatory Markers in Patients With Pneumonia

Despite treatment advances for sepsis and pneumonia, significant improvements in outcome have not been realized. Antiplatelet therapy may improve outcome in pneumonia and sepsis. In this study, the authors show that ticagrelor reduced leukocytes with attached platelets as well as the inflammatory biomarker interleukin (IL)-6. Pneumonia patients receiving ticagrelor required less supplemental oxygen and lung function tests trended toward improvement. Disruption of the P2Y12 receptor in a murine model protected against inflammatory response, lung permeability, and mortality. Results indicate a mechanistic link between platelets, leukocytes, and lung injury in settings of pneumonia and sepsis, and suggest possible therapeutic approaches to reduce complications. (Targeting Platelet-Leukocyte Aggregates in Pneumonia With Ticagrelor [XANTHIPPE]; NCT01883869

Temporal variations in English Populations of a forest insect pest, the green spruce aphid (Elatobium abietinum), associated with the North Atlantic Oscillation and global warming

Based on an exceptionally long modern ecological dataset (41 years), it has been possible to show that warm weather in England associated with a positive North Atlantic Oscillation (NAO) index causes the spring migration of the green spruce aphid (Elatobium abietinum), a pest species of spruce trees (Picea) to start earlier, continue for longer and contain more aphids. An upward trend in the NAO index during the period 1966-2006 is associated with an increasing population size of E. abietinum. It is important to understand the mechanisms behind the population fluctuations, because this aphid causes considerable damage to Picea plantations. Present day weather associated fluctuations in forest insect pests may be useful analogues in understanding past pest outbreaks in forests

Mitochondrial DNA signals of late glacial recolonization of Europe from near Eastern refugia

Human populations, along with those of many other species, are thought to have contracted into a number of refuge areas at the height of the last Ice Age. European populations are believed to be, to a large extent, the descendants of the inhabitants of these refugia, and some extant mtDNA lineages can be traced to refugia in Franco-Cantabria (haplogroups H1, H3, V, and U5b1), the Italian Peninsula (U5b3), and the East European Plain (U4 and U5a). Parts of the Near East, such as the Levant, were also continuously inhabited throughout the Last Glacial Maximum, but unlike western and eastern Europe, no archaeological or genetic evidence for Late Glacial expansions into Europe from the Near East has hitherto been discovered. Here we report, on the basis of an enlarged whole-genome mitochondrial database, that a substantial, perhaps predominant, signal from mitochondrial haplogroups J and T, previously thought to have spread primarily from the Near East into Europe with the Neolithic population, may in fact reflect dispersals during the Late Glacial period, ?19–12 thousand years (ka) ago.<br/

The Influence of Natural Barriers in Shaping the Genetic Structure of Maharashtra Populations

BACKGROUND: The geographical position of Maharashtra state makes it rather essential to study the dispersal of modern humans in South Asia. Several hypotheses have been proposed to explain the cultural, linguistic and geographical affinity of the populations living in Maharashtra state with other South Asian populations. The genetic origin of populations living in this state is poorly understood and hitherto been described at low molecular resolution level. METHODOLOGY/PRINCIPAL FINDINGS: To address this issue, we have analyzed the mitochondrial DNA (mtDNA) of 185 individuals and NRY (non-recombining region of Y chromosome) of 98 individuals belonging to two major tribal populations of Maharashtra, and compared their molecular variations with that of 54 South Asian contemporary populations of adjacent states. Inter and intra population comparisons reveal that the maternal gene pool of Maharashtra state populations is composed of mainly South Asian haplogroups with traces of east and west Eurasian haplogroups, while the paternal haplogroups comprise the South Asian as well as signature of near eastern specific haplogroup J2a. CONCLUSIONS/SIGNIFICANCE: Our analysis suggests that Indian populations, including Maharashtra state, are largely derived from Paleolithic ancient settlers; however, a more recent (∼10 Ky older) detectable paternal gene flow from west Asia is well reflected in the present study. These findings reveal movement of populations to Maharashtra through the western coast rather than mainland where Western Ghats-Vindhya Mountains and Narmada-Tapti rivers might have acted as a natural barrier. Comparing the Maharastrian populations with other South Asian populations reveals that they have a closer affinity with the South Indian than with the Central Indian populations

Sustainability of biosimilars in europe: A delphi panel consensus with systematic literature review

Introduction: Biosimilars have the potential to enhance the sustainability of evolving health care systems. A sustainable biosimilars market requires all stakeholders to balance competition and supply chain security. However, there is significant variation in the policies for pricing, procurement, and use of biosimilars in the European Union. A modified Delphi process was conducted to achieve expert consensus on biosimilar market sustainability in Europe. Methods: The priorities of 11 stakeholders were explored in three stages: a brainstorming stage supported by a systematic literature review (SLR) and key materials identified by the participants; development and review of statements derived during brainstorming; and a facilitated roundtable discussion. Results: Participants argued that a sustainable biosimilar market must deliver tangible and transparent benefits to the health care system, while meeting the needs of all stakeholders. Key drivers of biosimilar market sustainability included: (i) competition is more effective than regulation; (ii) there should be incentives to ensure industry investment in biosimilar development and innovation; (iii) procurement processes must avoid monopolies and minimize market disruption; and (iv) principles for procurement should be defined by all stakeholders. However, findings from the SLR were limited, with significant gaps on the impact of different tender models on supply risks, savings, and sustainability. Conclusions: A sustainable biosimilar market means that all stakeholders benefit from appropriate and reliable access to biological therapies. Failure to care for biosimilar market sustainability may impoverish biosimilar development and offerings, eventually leading to increased cost for health care systems and patients, with fewer resources for innovation

OPA1-related dominant optic atrophy is not strongly influenced by mitochondrial DNA background

<p>Abstract</p> <p>Background</p> <p>Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) are the most frequent forms of hereditary optic neuropathies. LHON is associated with mitochondrial DNA (mtDNA) mutations whereas ADOA is mainly due to mutations in the OPA1 gene that encodes a mitochondrial protein involved in the mitochondrial inner membrane remodeling. A striking influence of mtDNA haplogroup J on LHON expression has been demonstrated and it has been recently suggested that this haplogroup could also influence ADOA expression. In this study, we have tested the influence of mtDNA backgrounds on OPA1 mutations.</p> <p>Methods</p> <p>To define the relationships between OPA1 mutations and mtDNA backgrounds, we determined the haplogroup affiliation of 41 French patients affected by OPA1-related ADOA by control-region sequencing and RFLP survey of their mtDNAs.</p> <p>Results</p> <p>The comparison between patient and reference populations did not revealed any significant difference.</p> <p>Conclusion</p> <p>Our results argue against a strong influence of mtDNA background on ADOA expression. These data allow to conclude that OPA1 could be considered as a "severe mutation", directly responsible of the optic atrophy, whereas OPA1-negative ADOA and LHON mutations need an external factor(s) to express the pathology (i.e. synergistic interaction with mitochondrial background).</p

Neuronal activity disrupts myelinated axon integrity in the absence of NKCC1b

Through a genetic screen in zebrafish, we identified a mutant with disruption to myelin in both the CNS and PNS caused by a mutation in a previously uncharacterized gene, slc12a2b, predicted to encode a Na+, K+, and Cl− (NKCC) cotransporter, NKCC1b. slc12a2b/NKCC1b mutants exhibited a severe and progressive pathology in the PNS, characterized by dysmyelination and swelling of the periaxonal space at the axon–myelin interface. Cell-type–specific loss of slc12a2b/NKCC1b in either neurons or myelinating Schwann cells recapitulated these pathologies. Given that NKCC1 is critical for ion homeostasis, we asked whether the disruption to myelinated axons in slc12a2b/NKCC1b mutants is affected by neuronal activity. Strikingly, we found that blocking neuronal activity completely prevented and could even rescue the pathology in slc12a2b/NKCC1b mutants. Together, our data indicate that NKCC1b is required to maintain neuronal activity–related solute homeostasis at the axon–myelin interface, and the integrity of myelinated axons

Globalisation from Above? Corporate Social Responsibility, the Workers' Party and the Origins of the World Social Forum

In its assessment of the origins and early development of the World Social Forum this article challenges traditional understandings of the Forum as representing ‘globalisation from below’. By tracing the intricate relations among elements of business, civil society, and the Workers’ Party in the first years of the Forum, this article reveals the major role played by a corporate movement stemming from the Brazilian democratisation process in the 1980s, and how this combined with the transformed agenda of the Workers’ Party as it gained higher political offices to constrain the Forum’s activities from the outset. In so doing, this article challenges not only widespread conceptions of the Forum as a counter‐hegemonic alternative but also current critiques concerning its subsequent limitations. Furthermore, it reveals how traditional understandings of the World Social Forum and of global civil society are underpinned by flawed assumptions which typecast political activities in the global ‘South’

Fifteen years of the Australian imaging, biomarkers and lifestyle (AIBL) study: Progress and observations from 2,359 older adults spanning the spectrum from cognitive normality to Alzheimer\u27s disease

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer\u27s disease dementia (AD)) as an \u27Inception cohort\u27 who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an \u27Enrichment cohort\u27 (as of 10 April 2019). Objective: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. Methods: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance imaging, MRI; positron emission tomography, PET), biofluid biomarkers and lifestyle evaluations. Results: AIBL has made major contributions to the understanding of the natural history of AD, with cognitive and biological definitions of its three major stages: preclinical, prodromal and clinical. Early deployment of Aβ-amyloid and tau molecular PET imaging and the development of more sensitive and specific blood tests have facilitated the assessment of genetic and environmental factors which affect age at onset and rates of progression. Conclusion: This fifteen-year study provides a large database of highly characterized individuals with longitudinal cognitive, imaging and lifestyle data and biofluid collections, to aid in the development of interventions to delay onset, prevent or treat AD. Harmonization with similar large longitudinal cohort studies is underway to further these aims