Cooling therapy for acute stroke

Abstract BACKGROUND: Recent studies in acute stroke patients have shown an association between body temperature and prognosis. OBJECTIVES: Our objective was to assess the effects of cooling when applied to patients with acute ischaemic stroke or primary intracerebral haemorrhage. SEARCH STRATEGY: We searched the Cochrane Stroke Group's trial register (last searched in March 1999), plus MEDLINE searched up to November 1998 and EMBASE searched from January 1980 to November 1998. We contacted investigators, pharmaceutical companies and manufacturers of cooling equipment in this field. SELECTION CRITERIA: All completed randomised controlled trials or controlled clinical trials, published or unpublished, where cooling therapy (therapy given by physical devices or antipyretic drugs primarily to lower body temperature independently of basal temperature at the beginning of treatment) was applied up to two weeks of an acute ischaemic stroke or primary intracerebral haemorrhage. DATA COLLECTION AND ANALYSIS: Two reviewers independently searched for relevant trials. MAIN RESULTS: No randomised trials or controlled trials were identified; one placebo-controlled trial of metamizol is currently underway. REVIEWER'S CONCLUSIONS: There is currently no evidence from randomised trials to support the routine use of physical or chemical cooling therapy in acute stroke. Since experimental studies showed a neuroprotective effect of hypothermia in cerebral ischaemia, and hypothermia appears to improve the outcome in patients with severe closed head injury, trials with cooling therapy in acute stroke are warranted

Effects of local hypothermia-rewarming on physiology, metabolism and inflammation of acutely injured human spinal cord.

In five patients with acute, severe thoracic traumatic spinal cord injuries (TSCIs), American spinal injuries association Impairment Scale (AIS) grades A-C, we induced cord hypothermia (33 °C) then rewarming (37 °C). A pressure probe and a microdialysis catheter were placed intradurally at the injury site to monitor intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue metabolism and inflammation. Cord hypothermia-rewarming, applied to awake patients, did not cause discomfort or neurological deterioration. Cooling did not affect cord physiology (ISP, SCPP), but markedly altered cord metabolism (increased glucose, lactate, lactate/pyruvate ratio (LPR), glutamate; decreased glycerol) and markedly reduced cord inflammation (reduced IL1β, IL8, MCP, MIP1α, MIP1β). Compared with pre-cooling baseline, rewarming was associated with significantly worse cord physiology (increased ICP, decreased SCPP), cord metabolism (increased lactate, LPR; decreased glucose, glycerol) and cord inflammation (increased IL1β, IL8, IL4, IL10, MCP, MIP1α). The study was terminated because three patients developed delayed wound infections. At 18-months, two patients improved and three stayed the same. We conclude that, after TSCI, hypothermia is potentially beneficial by reducing cord inflammation, though after rewarming these benefits are lost due to increases in cord swelling, ischemia and inflammation. We thus urge caution when using hypothermia-rewarming therapeutically in TSCI

Epitaxially grown p‐type silicon wafers ready for cell efficiencies exceeding 25%

Combining the advantages of a high‐efficiency solar cell concept and a low carbon footprint base material is a promising approach for highly efficient, sustainable, and cost‐effective solar cells. In this work, we investigate the suitability of epitaxially grown p‐type silicon wafers for solar cells with tunnel oxide passivating contact rear emitter. As a first proof of principle, an efficiency limiting bulk recombination analysis of epitaxially grown p‐type silicon wafers deposited on high quality substrates (EpiRef) unveils promising cell efficiency potentials exceeding 25% for three different base resistivities of 3, 14, and 100 Ω cm. To understand the remaining limitations in detail, concentrations of metastable defects Fe i , CrB and BO are assessed by lifetime‐calibrated photoluminescence imaging and their impact on the overall recombination is evaluated. The EpiRef wafers’ efficiency potential is tracked along the solar cell fabrication process to quantify the impact of high temperature treatments on the material quality. We observe large areas with few structural defects on the wafer featuring lifetimes exceeding 10 ms and an efficiency potential of 25.8% even after exposing the wafer to a thermal oxidation at 1050 °C

Multiplication of microbes below 0.690 water activity: implications for terrestrial and extraterrestrial life

Since a key requirement of known life-forms is available water (water-activity; aw), searches for signatures of past life in terrestrial and extraterrestrial environments have recently targeted places known to have contained significant quantities of biologically available water. The lower limit of water activity that enables cell division is ~0.605 which, until now, was only known to be exhibited by a single eukaryote; the sugar-tolerant, fungal xerophile Xeromyces bisporus. The first forms of life on Earth were, however, prokaryotic. Furthermore, early life on Earth inhabited high-salt environments, suggesting an ability to withstand low water activity. Recent evidence indicates that some halophilic Archaea and Bacteria have water activity limits more or less equal to those of X. bisporus. Regardless of species, cellular systems are sensitive to minute differences in water activity (of w-units) so there is a need to determine water-activity values to three decimal places. We discuss water activity in relation to the limits of Earth’s present-day biosphere; the possibility of microbial multiplication by utilizing water from thin, aqueous films or non-liquid sources; whether prokaryotes were the first organisms able to multiply at the 0.605-aw limit; and whether extraterrestrial aqueous milieu of ≥0.605 aw can resemble fertile microbial habitats found on Earth

Tetherin Restricts Productive HIV-1 Cell-to-Cell Transmission

The IFN-inducible antiviral protein tetherin (or BST-2/CD317/HM1.24) impairs release of mature HIV-1 particles from infected cells. HIV-1 Vpu antagonizes the effect of tetherin. The fate of virions trapped at the cell surface remains poorly understood. Here, we asked whether tetherin impairs HIV cell-to-cell transmission, a major means of viral spread. Tetherin-positive or -negative cells, infected with wild-type or ΔVpu HIV, were used as donor cells and cocultivated with target lymphocytes. We show that tetherin inhibits productive cell-to-cell transmission of ΔVpu to targets and impairs that of WT HIV. Tetherin accumulates with Gag at the contact zone between infected and target cells, but does not prevent the formation of virological synapses. In the presence of tetherin, viruses are then mostly transferred to targets as abnormally large patches. These viral aggregates do not efficiently promote infection after transfer, because they accumulate at the surface of target cells and are impaired in their fusion capacities. Tetherin, by imprinting virions in donor cells, is the first example of a surface restriction factor limiting viral cell-to-cell spread

Characterisation of age and polarity at onset in bipolar disorder

Background Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. Aims To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics. Method Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts. Results Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO. Conclusions AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses