Cardioprotective effects of sodium glucose cotransporter 2 inhibition in angiotensin II-dependent hypertension are mediated by the local reduction of sympathetic activity and inflammation

The cardioprotective effects of sodium glucose cotrasponter 2 (SGLT2) inhibitors seem to be independent from the effects on glycemic control, through little-known mechanisms. In this study, we investigate whether the cardioprotective effects of empagliflozin, a SGLT2 inhibitor, may be associated with myocardial sympathetic activity and inflammatory cell infiltration in an experimental model of angiotensin II-dependent hypertension. Angiotensin II (Ang II), Ang II plus Empagliflozin, physiological saline, or physiological saline plus empagliflozin were administered to Sprague Dawley rats for two weeks. Blood pressure was measured by plethysmographic method. Myocardial hypertrophy and fibrosis were analysed by histomorphometry, and inflammatory cell infiltration and tyrosine hydroxylase expression, implemented as a marker of sympathetic activity, were evaluated by immunohistochemistry. Ang II increased blood pressure, myocardial hypertrophy, fibrosis, inflammatory infiltrates and tyrosine hydroxylase expression, as compared to the control group. Empagliflozin administration prevented the development of myocardial hypertrophy, fibrosis, inflammatory infiltrates and tyrosine hydroxylase overexpression in Ang II-treated rats, without affecting blood glucose and the Ang II-dependent increase in blood pressure. These data demonstrate that the cardioprotective effects of SGLT2 inhibition in Ang II-dependent hypertension may result from the myocardial reduction of sympathetic activity and inflammation and are independent of the modulation of blood pressure and blood glucose levels

Detection of an intergalactic meteor particle with the 6-m telescope

On July 28, 2006 the 6-m telescope of the Special Astrophysical Observatory of the Russian Academy of Sciences recorded the spectrum of a faint meteor. We confidently identify the lines of FeI and MgI, OI, NI and molecular-nitrogen N_2 bands. The entry velocity of the meteor body into the Earth's atmosphere estimated from radial velocity is equal to 300 km/s. The body was several tens of a millimeter in size, like chondrules in carbon chondrites. The radiant of the meteor trajectory coincides with the sky position of the apex of the motion of the Solar system toward the centroid of the Local Group of galaxies. Observations of faint sporadic meteors with FAVOR TV CCD camera confirmed the radiant at a higher than 96% confidence level. We conclude that this meteor particle is likely to be of extragalactic origin. The following important questions remain open: (1) How metal-rich dust particles came to be in the extragalactic space? (2) Why are the sizes of extragalactic particles larger by two orders of magnitude (and their masses greater by six orders of magnitude) than common interstellar dust grains in our Galaxy? (3) If extragalactic dust surrounds galaxies in the form of dust (or gas-and-dust) aureoles, can such formations now be observed using other observational techniques (IR observations aboard Spitzer satellite, etc.)? (4) If inhomogeneous extragalactic dust medium with the parameters mentioned above actually exists, does it show up in the form of irregularities on the cosmic microwave background (WMAP etc.)?Comment: 9 pages, 6 EPS figure

Microglia jointly degrade fibrillar alpha-synuclein cargo by distribution through tunneling nanotubes

Microglia are the CNS resident immune cells that react to misfolded proteins through pattern recognition receptor ligation and activation of inflammatory pathways. Here, we studied how microglia handle and cope with alpha-synuclein (alpha-syn) fibrils and their clearance. We found that microglia exposed to alpha-syn establish a cellular network through the formation of F-actin-dependent intercellular connections, which transfer alpha-syn from overloaded microglia to neighboring naive microglia where the alpha-syn cargo got rapidly and effectively degraded. Lowering the alpha-syn burden attenuated the inflammatory profile of microglia and improved their survival. This degradation strategy was compromised in cells carrying the LRRK2 G2019S mutation. We confirmed the intercellular transfer of alpha-syn assemblies in microglia using organotypic slice cultures, 2-photon microscopy, and neuropathology of patients. Together, these data identify a mechanism by which microglia create an on-demand functional network in order to improve pathogenic alpha-syn clearance

Motor Decline in Clinically Presymptomatic Spinocerebellar Ataxia Type 2 Gene Carriers

BACKGROUND: Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxia type 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomatic gene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we tested presymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motor performance and their motor learning capabilities. METHODS AND FINDINGS: 28 presymptomatic spinocerebellar ataxia type 2 gene carriers and an equal number of control volunteers matched for age and gender participated in the study. Both groups were tested in a prism adaptation task known to be sensible to both motor performance and visuomotor learning deficits. Our results clearly show that although motor learning capabilities are intact, motor performance deficits are present even years before the clinical manifestation of the disease start. CONCLUSIONS: The results show a clear deficit in motor performance that can be detected years before the clinical onset of the disease. This motor performance deficit appears before any motor learning or clinical manifestations of the disease. These observations identify the performance coefficient as an objective and quantitative physiological biomarker that could be useful to assess the efficiency of different therapeutic agents

Cancer research across Africa: a comparative bibliometric analysis.

INTRODUCTION: Research is a critical pillar in national cancer control planning. However, there is a dearth of evidence for countries to implement affordable strategies. The WHO and various Commissions have recommended developing stakeholder-based needs assessments based on objective data to generate evidence to inform national and regional prioritisation of cancer research needs and goals. METHODOLOGY: Bibliometric algorithms (macros) were developed and validated to assess cancer research outputs of all 54 African countries over a 12-year period (2009-2020). Subanalysis included collaboration patterns, site and domain-specific focus of research and understanding authorship dynamics by both position and sex. Detailed subanalysis was performed to understand multiple impact metrics and context relative outputs in comparison with the disease burden as well as the application of a funding thesaurus to determine funding resources. RESULTS: African countries in total published 23 679 cancer research papers over the 12-year period (2009-2020) with the fractional African contribution totalling 16 201 papers and the remaining 7478 from authors from out with the continent. The total number of papers increased rapidly with time, with an annual growth rate of 15%. The 49 sub-Saharan African (SSA) countries together published just 5281 papers, of which South Africa's contribution was 2206 (42% of the SSA total, 14% of all Africa) and Nigeria's contribution was 997 (19% of the SSA total, 4% of all Africa). Cancer research accounted for 7.9% of all African biomedical research outputs (African research in infectious diseases was 5.1 times than that of cancer research). Research outputs that are proportionally low relative to their burden across Africa are paediatric, cervical, oesophageal and prostate cancer. African research mirrored that of Western countries in terms of its focus on discovery science and pharmaceutical research. The percentages of female researchers in Africa were comparable with those elsewhere, but only in North African and some Anglophone countries. CONCLUSIONS: There is an imbalance in relevant local research generation on the continent and cancer control efforts. The recommendations articulated in our five-point plan arising from these data are broadly focused on structural changes, for example, overt inclusion of research into national cancer control planning and financial, for example, for countries to spend 10% of a notional 1% gross domestic expenditure on research and development on cancer