Ischemic stroke is a common neurologic condition and can lead to significant long term disability and death. Observational studies have demonstrated worse outcomes in patients presenting with the extremes of blood pressure as well as with hemodynamic variability. Despite these associations, optimal hemodynamic management in the immediate period of ischemic stroke remains an unresolved issue, particularly in the modern era of revascularization therapies. While guidelines exist for BP thresholds during and after thrombolytic therapy, there is substantially less data to guide management during mechanical thrombectomy. Ideal blood pressure targets after attempted recanalization depend both on the degree of reperfusion achieved as well as the extent of infarction present. Following complete reperfusion, lower blood pressure targets may be warranted to prevent reperfusion injury and promote penumbra recovery however prospective clinical trials addressing this issue are warranted.

Summary Background Meiotic checkpoints ensure the production of gametes with the correct complement and integrity of DNA; in metazoans these pathways sense errors and transduce signals to trigger apoptosis to eliminate damaged germ cells. The extent to which checkpoints monitor and safeguard the genome differs between sexes and may contribute to the high frequency of human female meiotic errors. In the C. elegans female germ line, DNA damage, chromosome asynapsis and/or unrepaired meiotic double strand breaks (DSBs) activate checkpoints that induce apoptosis; conversely, male germ cells do not undergo apoptosis. Results Here we show that the recombination checkpoint is in fact activated in male germ cells despite the lack of apoptosis. The 9-1-1 complex and phosphatidylinositol 3-kinase-related protein kinase ATR, sensors of DNA damage, are recruited to chromatin in the presence of unrepaired meiotic DSBs in both female and male germ lines. Furthermore, checkpoint kinase CHK-1 is phosphorylated and p53 ortholog CEP-1 induces expression of BH3-only pro-apoptotic proteins in germ lines of both sexes under activating conditions. The core cell death machinery is expressed in female and male germ lines; however, CED-3 caspase is not activated in the male germ line. Although apoptosis is not triggered, checkpoint activation in males has functional consequences for gamete quality, as there is reduced viability of progeny sired by males with a checkpoint-activating defect in the absence of checkpoint function. Conclusions We propose that the recombination checkpoint functions in male germ cells to promote repair of meiotic recombination intermediates, thereby improving the fidelity of chromosome transmission in the absence of apoptosis.

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Objective:The mechanism of hypoglycorrhachia—low CSF glucose—in meningitis remains unknown. We sought to evaluate the relative contribution of CSF inflammation vs microorganisms (bacteria and fungi) in lowering CSF glucose levels.Methods:We retrospectively categorized CSF profiles into microbial and aseptic meningitis and analyzed CSF leukocyte count, glucose, and protein concentrations. We assessed the relationship between these markers using multivariate and stratified linear regression analysis for initial and repeated CSF sampling. We also calculated the receiver operating characteristics of CSF glucose and CSF-to-serum glucose ratios to presumptively diagnose microbial meningitis.Results:We found that increasing levels of CSF inflammation were associated with decreased CSF glucose levels in the microbial but not aseptic category. Moreover, elevated CSF protein levels correlated more strongly than the leukocyte count with low CSF glucose levels on initial (R2 = 36%, p < 0.001) and repeated CSF sampling (R2 = 46%, p < 0.001). Hypoglycorrhachia (<40 mg/dL) was observed in 50.1% of microbial cases, but only 9.6% of aseptic cases, most of which were neurosarcoidosis. Absolute CSF glucose and CSF-to-serum glucose ratios had similar low sensitivity and moderate-to-high specificity in diagnosing microbial meningitis at thresholds commonly used.Conclusions:The main driver of hypoglycorrhachia appears to be a combination of microbial meningitis with moderate to high degrees of CSF inflammation and proteins, suggesting that the presence of microorganisms capable of catabolizing glucose is a determinant of hypoglycorrhachia in meningitis. A major notable exception is neurosarcoidosis. Low CSF glucose and CSF-to-serum glucose ratios are useful markers for the diagnosis of microbial meningitis.