Neuroprotection or Increased Brain Damage Mediated by Temperature in Stroke Is Time Dependent

The control of temperature during the acute phase of stroke may be a new therapeutic target that can be applied in all stroke patients, however therapeutic window or timecourse of the temperature effect is not well established. Our aim is to study the association between changes in body temperature in the first 72 hours and outcome in patients with ischemic (IS) and hemorrhagic (ICH) stroke. We prospectively studied 2931 consecutive patients (2468 with IS and 463 with ICH). Temperature was obtained at admission, and at 24, 48 and 72 hours after admission. Temperature was categorized as low (<36°C), normal (36–37°C) and high (>37°C). As the main variable, we studied functional outcome at 3 months determined by modified Rankin Scale

Spectroscopic evidence for an all-ferrous [4Fe–4S]0 cluster in the superreduced activator of 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans

The key enzyme of the fermentation of glutamate by Acidaminococcus fermentans, 2-hydroxyglutarylcoenzyme A dehydratase, catalyzes the reversible syn-elimination of water from (R)-2-hydroxyglutaryl-coenzyme A, resulting in (E)-glutaconylcoenzyme A. The dehydratase system consists of two oxygen-sensitive protein components, the activator (HgdC) and the actual dehydratase (HgdAB). Previous biochemical and spectroscopic studies revealed that the reduced [4Fe–4S]+ cluster containing activator transfers one electron to the dehydratase driven by ATP hydrolysis, which activates the enzyme. With a tenfold excess of titanium(III) citrate at pH 8.0 the activator can be further reduced, yielding about 50% of a superreduced [4Fe–4S]0 cluster in the all-ferrous state. This is inferred from the appearance of a new Mössbauer spectrum with parameters δ = 0.65 mm/s and ΔEQ = 1.51–2.19 mm/s at 140 K, which are typical of Fe(II)S4 sites. Parallel-mode electron paramagnetic resonance (EPR) spectroscopy performed at temperatures between 3 and 20 K showed two sharp signals at g = 16 and 12, indicating an integer-spin system. The X-band EPR spectra and magnetic Mössbauer spectra could be consistently simulated by adopting a total spin St = 4 for the all-ferrous cluster with weak zero-field splitting parameters D = −0.66 cm−1 and E/D = 0.17. The superreduced cluster has apparent spectroscopic similarities with the corresponding [4Fe–4S]0 cluster described for the nitrogenase Fe-protein, but in detail their properties differ. While the all-ferrous Fe-protein is capable of transferring electrons to the MoFe-protein for dinitrogen reduction, a similar physiological role is elusive for the superreduced activator. This finding supports our model that only one-electron transfer steps are involved in dehydratase catalysis. Nevertheless we discuss a common basic mechanism of the two diverse systems, which are so far the only described examples of the all-ferrous [4Fe–4S]0 cluster found in biology

Use of short PTFE segments (&lt; 6 cm) compares favorably with pure autologous repair in failing or thrombosed native arteriovenous fistulas

Objective: The re-establishment of patency in a stenosed or thrombosed native arteriovenous fistula (AVF) is fundamental to regaining adequate hemodialysis through the same cannulable vein. Many surgeons have been reluctant to use even small segments of synthetic grafts in AVF revisions because of a perception that these would lead to poor results; however, studies comparing various treatment options are scarce. This study compared the use of short (&lt;6 cm) polytetrafluoroethylene (PTFE) segments with pure autologous repair in stenosed or thrombosed native fistulas. Methods. The cumulative postintervention primary patency rates of two groups of hemodialysis patients receiving different surgical revision operations of their vascular accesses were prospectively compared. Group I (n = 30) comprised patients who presented with stenosed or thrombosed native fistulas and received short (2 to 6 cm) interposition PTFE grafts placed after the stenosed or thrombosed outflow vein segment was resected. These short PTFE grafts were not used for cannulation. Group II (n = 29) comprised patients who presented with dysfunctional or failed AVFs and underwent various types of pure autogenous corrections. AVF dysfunction or thrombosis was detected with clinical examination and color duplex ultrasound scanning. In all cases, on-table arteriography-fistulography was performed before surgical repair. Access adequacy was assessed in all patients postoperatively after the first puncture and every month thereafter (mean follow up 16.7 months). Results: No statistically significant difference in patency was observed between the two groups. Postintervention cumulative patencies were 100%, 88%, and 82% for group I and 90%, 82%, and 71% for group II at 6, 12, and 18 months, respectively (P =.8). Conclusions. Short (&lt; 6 cm) interposition PTFE segments used for the revision of failing or failed AVFs compare favorably to purely native repair and do not alter the autologous behavior of the initial access. These short PTFE revisions resulted in satisfactory midterm primary patency without further consumption of the venous capital by harvesting segments of vein from other locations and without compromising more proximal access sites. This practice is recommended and is justified as part of an aggressive access salvage policy addressed by many authors so far

Structural and functional characteristics of color vision changes in choroideremia

Color vision is considered a marker of cone function and its assessment in patients with retinal pathology is complementary to the assessments of spatial vision [best-corrected visual acuity (BCVA)] and contrast detection (perimetry). Rod-cone and chorioretinal dystrophies-such as choroideremia-typically cause alterations to color vision, making its assessment a potential outcome measure in clinical trials. However, clinical evaluation of color vision may be compromised by pathological changes to spatial vision and the visual field. The low vision Cambridge Color Test (lvCCT) was developed specifically to address these latter issues. We used the trivector version of the lvCCT to quantify color discrimination in a cohort of 53 patients with choroideremia. This test enables rapid and precise characterization of color discrimination along protan, deutan, and tritan axes more reliably than the historically preferred test for clinical trials, namely the Farnsworth Munsell 100 Hue test. The lvCCT demonstrates that color vision defects-particularly along the tritan axis-are seen early in choroideremia, and that this occurs independent of changes in visual acuity, pattern electroretinography and ellipsoid zone area on optical coherence tomography (OCT). We argue that the selective loss of tritan color discrimination can be explained by our current understanding of the machinery of color vision and the pathophysiology of choroideremia