Ambient temperature and kidney function in primary care patients

Introduction Exposure to high ambient temperatures is associated with a risk of acute kidney injury. However, evidence comes from emergency departments or extreme weather exposures. It is unclear whether temperature-related adverse kidney outcomes can also be detected at a community level in a temperate climate zone. Methods In a 9.5-year retrospective cohort study we correlated estimated glomerular filtration rate (eGFR) values of Swiss adult primary care patients from the FIRE cohort (Family medicine Research using Electronic medical records) with same-day maximum local ambient temperature data. We investigated 5 temperature groups (< 15 °C, 15–19 °C, 20–24 °C, 25–29 °C and  ≥ 30 °C) as well as possible interactions for patients with increased kidney vulnerability (chronic heart failure, diabetes, chronic kidney disease, therapy with renin–angiotensin–aldosterone-system (RAAS) inhibitors, diuretics or non-steroidal anti-inflammatory drugs). Results We included 18,000 primary care patients who altogether provided 132,176 creatinine measurements. In the unadjusted analysis, higher ambient temperatures were associated with lower eGFR across all age and vulnerability groups. In the adjusted models, we did not find a consistent association.The highest ambient temperature differences (> 25 or > 30 versus < 15 °C) were associated with marginally reduced kidney function only in patients with ≥ 3 risk factors for kidney vulnerability, with a maximum estimated glomerular filtration rate reduction of −2.9 ml/min/1.73m$^{2}$ (SE 1.0), P 0.003. Discussion In a large primary care cohort from a temperate climate zone, we did not find an association between ambient temperatures and kidney function. A marginal inverse association in highly vulnerable patients is of unclear clinical relevance

Mechanistic basis of choline import involved in teichoic acids and lipopolysaccharide modification

Phosphocholine molecules decorating bacterial cell wall teichoic acids and outer-membrane lipopolysaccharide have fundamental roles in adhesion to host cells, immune evasion, and persistence. Bacteria carrying the operon that performs phosphocholine decoration synthesize phosphocholine after uptake of the choline precursor by LicB, a conserved transporter among divergent species.; Streptococcus pneumoniae; is a prominent pathogen where phosphocholine decoration plays a fundamental role in virulence. Here, we present cryo-electron microscopy and crystal structures of; S. pneumoniae; LicB, revealing distinct conformational states and describing architectural and mechanistic elements essential to choline import. Together with in vitro and in vivo functional characterization, we found that LicB displays proton-coupled import activity and promiscuous selectivity involved in adaptation to choline deprivation conditions, and describe LicB inhibition by synthetic nanobodies (sybodies). Our results provide previously unknown insights into the molecular mechanism of a key transporter involved in bacterial pathogenesis and establish a basis for inhibition of the phosphocholine modification pathway across bacterial phyla

Treatment of Relapsing Paralysis in Experimental Encephalomyelitis by Targeting Th1 Cells through Atorvastatin

Statins, known as inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, exhibit numerous functions related to inflammation, such as MHC class II down-regulation, interference with T cell adhesion, and induction of apoptosis. Here we demonstrate that both subcutaneous and oral administration of atorvastatin inhibit the development of actively induced chronic experimental autoimmune encephalomyelitis in SJL/J mice and significantly reduce the inflammatory infiltration into the central nervous system (CNS). When treatment was started after disease onset, atorvastatin reduced the incidence of relapses and protected from the development of further disability. Both the reduced autoreactive T cell response measured by proliferation toward the encephalitogenic peptide PLP139–151 and the cytokine profile indicate a potent blockade of T helper cell type 1 immune response. In in vitro assays atorvastatin not only inhibited antigen-specific responses, but also decreased T cell proliferation mediated by direct TCR engagement independently of MHC class II and LFA-1. Inhibition of proliferation was not due to apoptosis induction, but linked to a negative regulation on cell cycle progression. However, early T cell activation was unaffected, as reflected by unaltered calcium fluxes. Thus, our results provide evidence for a beneficial role of statins in the treatment of autoimmune attack on the CNS

Learning, Computing, and Trustworthiness in Intelligent IoT Environments: Performance-Energy Tradeoffs

An Intelligent IoT Environment (iIoTe) is comprised of heterogeneous devices that can collaboratively execute semi-autonomous IoT applications, examples of which include highly automated manufacturing cells or autonomously interacting harvesting machines. Energy efficiency is key in such edge environments, since they are often based on an infrastructure that consists of wireless and battery-run devices, e.g., e-tractors, drones, Automated Guided Vehicle (AGV)s and robots. The total energy consumption draws contributions from multipleiIoTe technologies that enable edge computing and communication, distributed learning, as well as distributed ledgers and smart contracts. This paper provides a state-of-the-art overview of these technologies and illustrates their functionality and performance, with special attention to the tradeoff among resources, latency, privacy and energy consumption. Finally, the paper provides a vision for integrating these enabling technologies in energy-efficient iIoTe and a roadmap to address the open research challengesComment: Accepted for publication in IEEE Transactions on Green Communication and Networkin

Impact of gigahertz and terahertz transport regimes on spin propagation and conversion in the antiferromagnet IrMn

Control over spin transport in antiferromagnetic systems is essential for future spintronic applications with operational speeds extending to ultrafast time scales. Here, we study the transition from the gigahertz (GHz) to terahertz (THz) regime of spin transport and spin-to-charge current conversion (S2C) in the prototypical antiferromagnet IrMn by employing spin pumping and THz spectroscopy techniques. We reveal a factor of 4 shorter characteristic propagation lengths of the spin current at THz frequencies (∼0.5 nm) as compared to GHz experiments (∼2 nm). This observation may be attributed to different transport regimes. The conclusion is supported by extraction of sub-picosecond temporal dynamics of the THz spin current. We identify no relevant impact of the magnetic order parameter on S2C signals and no scalable magnonic transport in THz experiments. A significant role of the S2C originating from interfaces between IrMn and magnetic or non-magnetic metals is observed, which is much more pronounced in the THz regime and opens the door for optimization of the spin control at ultrafast time scales