SVEP1 plays a crucial role in epidermal differentiation

SVEP1 is a recently identified multidomain cell adhesion protein, homologous to the mouse polydom protein, which has been shown to mediate cell‐cell adhesion in an integrin‐dependent manner in osteogenic cells. In this study, we characterized SVEP1 function in the epidermis. SVEP1 was found by qRT‐PCR to be ubiquitously expressed in human tissues, including the skin. Confocal microscopy revealed that SVEP1 is normally mostly expressed in the cytoplasm of basal and suprabasal epidermal cells. Downregulation of SVEP1 expression in primary keratinocytes resulted in decreased expression of major epidermal differentiation markers. Similarly, SVEP1 downregulation was associated with disturbed differentiation and marked epidermal acanthosis in three‐dimensional skin equivalents. In contrast, the dispase assay failed to demonstrate significant differences in adhesion between keratinocytes expressing normal vs low levels of SVEP1. Homozygous Svep1 knockout mice were embryonic lethal. Thus, to assess the importance of SVEP1 for normal skin homoeostasis in vivo, we downregulated SVEP1 in zebrafish embryos with a Svep1‐specific splice morpholino. Scanning electron microscopy revealed a rugged epidermis with perturbed microridge formation in the centre of the keratinocytes of morphant larvae. Transmission electron microscopy analysis demonstrated abnormal epidermal cell‐cell adhesion with disadhesion between cells in Svep1‐deficient morphant larvae compared to controls. In summary, our results indicate that SVEP1 plays a critical role during epidermal differentiation.     

Augmentation of low-frequency ultrasound-induced clot disruption by hydroxyethyl starch is dependent on the duration and intensity of ultrasound exposure; an in vitro study

We investigated the synergistic effect between low-frequency ultrasound (US) and hydroxyethyl starch (HAES) on blood clot disruption, using different HAES concentrations, US duration and intensity. Human blood clots, 200 to 400 mg in weight, were placed in tubes containing 10 mL of normal saline alone or with HAES 0.1%, 1% or 2%. Clots were randomized to four intensities of US exposure: none, low, medium and high (maximal amplitude of motion at the tip of the horn: 0, 96, 144 and 192 micro m, respectively), and for three durations of US exposure (10, 20 and 40 s). After treatment, the clots were reweighed, and the percent differences in weights were calculated. US intensity, US duration and HAES concentration had a significant effect on the blood clot dissolution (p < 0.001 for all three variables). HAES augmented clot dissolution only when US intensity was medium or high. With low intensity, HAES did not augment clot lysis. CONCLUSIONS: microparticle-containing solutions, such as HAES, have a potential for augmenting clot disruption by US. This effect is highly dependent on US intensity.     

Risk of mortality with a bloodstream infection is higher in the less severely ill at admission

RATIONALE: Health care-associated bloodstream infections are common in critically ill patients; however, investigators have had difficulty in quantifying the clinical impact of these infections given the high expected mortality among these patients. OBJECTIVE: To estimate the impact of health care-associated bloodstream infections on in-hospital mortality after adjusting for severity of illness at critical care admission. METHOD: A cohort of medical and surgical intensive care unit patients. MEASUREMENTS: Severity of illness at admission, bloodstream infection, and in-hospital mortality. MAIN RESULTS: Among the 2,783 adult patients, 269 developed unit-associated bloodstream infections. After adjusting for severity of illness, patients with a lower initial severity of illness who developed an infection had a greater than twofold higher risk for in-hospital mortality (hazard ratio [HR] = 2.42, 95% confidence interval [CI] 1.70, 3.44) when compared with patients without infection and with a similar initial severity of illness. In contrast, patients with a higher initial severity of illness who subsequently developed an infection did not have an increased risk for in-hospital mortality (HR = 0.96, 95%CI 0.76, 1.23) when compared with patients without infection but with a similar initial severity of illness. CONCLUSIONS: These results suggest that these infections in less ill patients have a higher attributable impact on subsequent mortality than in more severely ill patients. Focusing interventions to prevent bloodstream infections in less severely ill patients would be expected to have a greater benefit in terms of mortality reduction.     

Solvent-induced selectivity of Williamson etherification in the pursuit of amides resistant against oxidative degradation

This article reports two discoveries. (1) 2-Methoxyethanol induces unprecedented selectivity for etherification of 5-hydroxy-2-nitrobenzic acids without forming undesired esters. (2) Such compounds are precursors for amides showing unusual robustness against oxidative degradation, essential for molecular electrets that transfer strongly oxidizing holes at about −6.4 eV vs. vacuum.

Selective etherification produces precursors for amides resistant to oxidative degradation, i.e., showing reversible oxidation at 1.5 to 1.7 V vs. SCE.     

EEG Abnormalities in Children with a First Unprovoked Seizure

Summary: We examined EEG findings from an ongoing study of 347 children with a first unprovoked seizure. EEGs were available in 321 (93%), and 135 (42%) had an abnormal EEG. EEG abnormalities included focal spikes (n = 77), generalized spike and wave discharges (n = 28), slowing (n = 43), and nonspecific abnormalities (n = 7). Abnormal EEGs were more common in children with remote symptomatic seizures (60%) than in those with idiopathic seizures (38%) (p < 0.003), more common in partial seizures (56%) than in generalized seizures (35%) (p < 0.001), and more common in children age >3 years (52%) than in younger children (12%) (p < 0.001). Records including both awake and sleep tracings were available in 148 (46%) cases. For 122 (38%) only awake tracings and for 51 (16%) only sleep tracings were available. Fifty-nine (40%) of the 148 patients with both an awake and asleep tracing had abnormal EEGs. Of 50 such EEGs with epileptiform abnormalities, 15 (30%) demonstrated the abnormality either only while awake (n = 8) or only while asleep (n = 7). Of 17 patients with EEG slowing, 8 showed slowing only in the awake tracing and 9 showed slowing in both the awake and asleep tracing. Children with even a single unprovoked seizure have a high incidence of EEG abnormalities. Obtaining a combined awake and sleep EEG significantly increases the yield of EEG abnormalities. In children with an idiopathic first seizure, EEG abnormalities are associated with an increased risk of seizure recurrence.     

Nicardipine Associated Risk of Short-Term Mortality in Critically Ill Patients with Ischemic Stroke

Background: Hypertensive emergency is commonly associated with acute ischemic stroke and can be a predictor of poor outcome in these patients. Nicardipine and labetalol are commonly administered for the treatment of acute hypertension following stroke. Yet, data are lacking on the safety of these agents in this setting. Objective: This study aimed to determine all-cause in-hospital mortality, medication-related hypotensive episodes, development of hospital acquired infections and hospital length of stay between nicardipine and labetalol use for the management of hypertension after acute ischemic stroke. Methods: This retrospective study used a prospective database of individuals admitted to the neurointensive care unit at a university-based hospital over 39 months. Patients with confirmed ischemic strokes were included in this analysis. Data were recorded for administration of nicardipine and labetalol following acute stroke. Results: A total of 244 patients with acute ischemic stroke were included in this analysis (mean age, 64.3 ± 15 years; 52.2% males). Nicardipine use after acute ischemic stroke was associated with an increased risk of 30-day mortality (odds ratio [OR]: 4.6, 95% confidence interval [CI] 1.3-15.7; P = .02). A single episode of hypotension in the first 72hours of admission was also significantly associated with mortality (OR 4.35 [95% CI 1.2-14.9]; P = .02). Conclusions: Nicardipine was associated with an increased risk of short-term mortality after acute ischemic stroke. This may have been due to hypotension, tachycardia, or pulmonary edema which were not apparent in our study. Further studies are required to elucidate the cause of this association.     

急性心肌梗死冠状动脉自发再通对心室晚电位的影响

137例急性心肌梗死病人发病后1周内做冠脉造影。冠脉完全闭塞65例(组1),不全闭塞72例(组2),冠脉自发再通率为53%。组2晚电位检出率显著低于组1,左室射血分数显著高于组1。逐步多元回归分析示肌酸激酶峰值及冠脉持续闭塞为影响晚电位检出率的两个自变量(皆 P<0.05)。