Relationship between resting 201Tl reverse redistribution, microvascular perfusion, and functional recovery in acute myocardial infarction.

201TI reverse redistribution is a common finding early after reperfusion therapy for myocardial infarction. Its mechanism and clinical implications remain unclear. The aim of this study was to clarify the relationships between reverse redistribution, microvascular perfusion, and myocardial viability. METHODS: Resting, 10-min-postinjection, and redistribution 201TI data obtained for 33 patients 8 and 42 d after the onset of acute myocardial infarction were compared with echocardiographic wall motion measured acutely and on day 42. Microvascular perfusion was assessed by myocardial contrast echocardiography performed 10 min after restoration of complete patency of the infarct artery. RESULTS: Marked significant reverse redistribution was found on day 8 (absolute change, 7.5%+/-7.9% of the 10-min-postinjection defect size; P<5x0.000001) and significantly decreased on day 42 (2.7%+/-6.8%; P = 0.004 between days 8 and 42). The 10-min-postinjection defect size best predicted the final infarct size on day 42 and was closely related to microvascular perfusion. Patients with adequate reperfusion had a smaller postinjection defect on day 8 (21.1%+/-14.6%) and a larger reverse redistribution (10.2%+/-6.1%) than did patients with no reflow (35.3%+/-13% and 3.2%+/-9.2%, respectively; P<0.04 for both). CONCLUSION: Reverse redistribution was marked early after myocardial infarction in patients with complete patency of the infarct artery and decreased in subsequent weeks. Reverse redistribution was associated with restoration of adequate microvascular reperfusion and with myocardial salvage and viability. The early postinjection scans on day 8 were the relevant images for assessing myocardial salvage and predicting wall motion recovery.     

Modulatory Role of Nitric Oxide/cGMP System in Endothelin-1-Induced Signaling Responses in Vascular Smooth Muscle Cells

Nitric oxide (NO) is an important vasoprotective molecule that serves not only as a vasodilator but also exerts antihypertrophic and antiproliferative effects in vascular smooth muscle cells (VSMC). The precise mechanism by which the antihypertrophic and antiproliferative responses of NO are mediated remains obscure. However, recent studies have suggested that one of the mechanisms by which this may be achieved includes the attenuation of signal transduction pathways responsible for inducing the hypertrophic and proliferative program in VSMC. Endothelin-1 is a powerful vasoconstrictor peptide with mitogenic and growth stimulatory properties and exerts its effects by activating multiple signaling pathways which include ERK 1/2, PKB and Rho-ROCK. Both cGMP-dependent and independent events have been reported to mediate the effect of NO on these pathways leading to its vasoprotective response. This review briefly summarizes some key studies on the modulatory effect of NO on these signaling pathways and discusses the possible role of cGMP system in this process.     

Association of Schistosoma haematobium infection with protection against acute Plasmodium falciparum malaria in Malian children

Plasmodium falciparum and Schistosoma haematobium are co-endemic parasitic diseases with worldwide distribution. Evidence suggests interactions occur between helminthic and malaria infections, although it is unclear whether this effect is beneficial or harmful to the host. Malian children 4-14 years of age with asymptomatic S. haematobium infection (SP) (n = 338) were prospectively matched by age, sex, and residence to children without schistosomiasis (SN) (n = 338) who were cleared of occult intestinal parasites, and followed-up for one malaria transmission season (25 weeks). The time to the first clinical malaria infection, incidence of malaria episodes, and parasitemia were recorded. Age associated protection from malaria in children with schistosomiasis was observed. SP children (4-8 years of age) compared with SN children demonstrated delayed time to first clinical malaria infection (74 versus 59 days; P = 0.04), fewer numbers of malaria episodes (1.55 versus 1.81 infections; P = 0.03) and lower geometric mean parasite densities (6,359 versus 9,874 asexual forms/mm(3); P = 0.07) at first infection. No association between schistosomiasis and P. falciparum malaria was observed in children 9-14 years of age. We conclude that underlying schistosomiasis is associated with protection against clinical falciparum malaria in an age-dependent manner.     

Porous sorbents for the capture of radioactive iodine compounds: a review

The number of studies on the capture of radioactive iodine compounds by porous sorbents has regained major importance in the last few years. In fact, nuclear energy is facing major issues related to operational safety and the treatment and safe disposal of generated radioactive waste. In particular during nuclear accidents, such as that in 2011 at Fukushima, gaseous radionuclides have been released in the off-gas stream. Among these, radionuclides that are highly volatile and harmful to health such as long-lived ¹²⁹I, short-lived ¹³¹I and organic compounds such as methyl iodide (CH₃I) have been released. Immediate and effective means of capturing and storing these radionuclides are needed. In the present review, we focus on porous sorbents for the capture and storage of radioactive iodine compounds. Concerns with, and limitations of, the existing sorbents with respect to operating conditions and their capacities for iodine capture are discussed and compared.

In the capture of radioactive iodine compounds by porous sorbents, concerns with, and limitations of, the existing sorbents with respect to operating conditions and their capacities for iodine capture are discussed and compared.     

Risk of Venous Thromboembolism in Patients with Large Hemispheric Infarction Undergoing Decompressive Hemicraniectomy

Background

Deep-venous thrombosis (DVT) and pulmonary embolism (PE) are major causes of morbidity and mortality in patients with acute ischemic stroke. This study is the first to examine the risk of venous thromboembolism in patients with large hemispheric infarction undergoing decompressive hemicraniectomy.

Methods

The study population included 95 consecutive patients with a large hemispheric infarction who underwent decompressive hemicraniectomy between 2006 and 2014 at our institution. All patients received prophylactic unfractionated heparin and intermittent compression devices (SCD). Patients were systematically screened for DVT at 5-day interval using Duplex ultrasound. PE was diagnosed on chest CT angiography.

Results

Mean age was 57 ± 12 years; mean BMI was 28.3 ± 7.4 kg/m². 30.5 % of patients had infarction in the dominant hemisphere and 69.5 % in the non-dominant hemisphere. The mean NIHSS score was 16.0 ± 5 at admission. The mean length of stay was 22 ± 17 days. 35 % of patients developed a DVT including 27 % who developed above-knee DVT and required placement of an inferior vena cava filter. In multivariable analysis, predictors of DVT were an NIHSS ≥ 17 (p = 0.007), seizures (p = 0.003), hypertension (p = 0.03), and increasing length of stay (p = 0.01). The proportion of patients who developed PE was 13 %. In multivariate analysis, BMI ≥ 30 predicted PE (p = 0.05).

Conclusions

The rate of DVT and PE is remarkably high in patients with large hemispheric infarction undergoing decompressive hemicraniectomy despite prophylactic measures. We recommend routine screening for DVT in this population. Interventions beyond the standard prophylactic measures may be necessary in this high-risk group.

     

ErbB2 receptor controls microtubule capture by recruiting ACF7 to the plasma membrane of migrating cells

Microtubules (MTs) contribute to key processes during cell motility, including the regulation of focal adhesion turnover and the establishment and maintenance of cell orientation. It was previously demonstrated that the ErbB2 receptor tyrosine kinase regulated MT outgrowth to the cell cortex via a complex including Memo, the GTPase RhoA, and the formin mDia1. But the mechanism that linked this signaling module to MTs remained undefined. We report that ErbB2-induced repression of glycogen synthase kinase-3 (GSK3) activity, mediated by Memo and mDia1, is required for MT capture and stabilization. Memo-dependent inhibition of GSK3 allows the relocalization of APC (adenomatous polyposis coli) and cytoplasmic linker-associated protein 2 (CLASP2), known MT-associated proteins, to the plasma membrane and ruffles. Peripheral microtubule extension also requires expression of the plus-end binding protein EB1 and its recently described interactor, the spectraplakin ACF7. In fact, in migrating cells, ACF7 localizes to the plasma membrane and ruffles, in a Memo-, GSK3-, and APC-dependent manner. Finally, we demonstrate that ACF7 targeting to the plasma membrane is both required and sufficient for MT capture downstream of ErbB2. This function of ACF7 does not require its recently described ATPase activity. By defining the signaling pathway by which ErbB2 allows MT capture and stabilization at the cell leading edge, we provide insights into the mechanism underlying cell motility and steering.     

Cell-mediated immunity elicited by the blood stage malaria vaccine apical membrane antigen 1 in Malian adults: Results of a Phase I randomized trial

The development of a safe and effective malaria vaccine is impeded by the complexity of the Plasmodium life cycle. A vaccine that elicits both cell-mediated and humoral immune responses might be needed for protection against this multistage parasitic infection. Apical membrane antigen 1 (AMA-1) plays a key role in erythrocytic invasion but is also expressed in sporozoites and in late stage liver schizonts, where it may provide a target of protective cell-mediated immunity (CMI). A Phase 1 trial of a vaccine consisting of recombinant AMA-1 protein and the Adjuvant system AS02A was conducted in 60 Malian adults aged 18–55 years who were randomized to receive either half-dose (25 μg/0.25 ml) or full dose (50 μg/0.5 ml) FMP2.1/AS02A or a control rabies vaccine. Interleukin 5 (IL-5) and interferon-γ (IFN-γ) production as evaluated by ELISpot and lymphocyte proliferation were measured after in vitro AMA-1 stimulation of peripheral blood mononuclear cells (PBMCs) collected on Days 0 and 90. Post-FMP2.1/AS02A immunization mean stimulation indices were significantly elevated as were the number of IL-5 spot forming cells (SFC)/10⁶ PBMC, but no difference was noted in INF-γ production between the AMA-1/AS02A vaccinated group and the rabies group. These results provide evidence that complex immune responses can be induced by this vaccination strategy and add further impetus for the continuing clinical evaluation of this vaccine.     

Predictors of Disordered Eating in Young Males

Recent findings suggest that disordered eating (DE) symptomatology may be underestimated in the male population. The present study examined depressive symptomatology as a potential mediator of the relationships between body image dissatisfaction, strategies to change body weight and muscles, media pressure, and DE (emotional, restrained and emotional eating) in 260 male undergraduates who completed a self-reported questionnaire. Path analyses indicated that media influence and strategies to decrease body weight had direct positive effects on depressive symptomatology, which in turn predicted emotional eating. Media influence had a direct positive effect on emotional eating, whereas strategies to decrease body weight did not exhibit a direct effect on emotional eating. Therefore, the latter pathway was removed from the model. The link between media pressure, strategies to decrease body weight and emotional eating was partially mediated by depressive symptomatology. The present findings can inform the development and implementation of prevention and education programs for DE in schools and universities.     

Endoscopic balloon dilation of ileal pouch strictures

BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of choice in patients with ulcerative colitis. Strictures can occur at the inlet and outlet of the pouch. Endoscopic balloon dilation has been successfully used in patients with Crohn's strictures at the small intestine and colon. There are no published trials on endoscopic balloon therapy of ileal pouch strictures. AIM: To evaluate outpatient endoscopic balloon dilation of strictures in ileal pouches. METHODS: Patients underwent nonfluoroscopy-guided, nonsedated, outpatient endoscopic dilations with an 8.6-mm upper endoscope and through-the-scope balloons (size: 11-18 mm). Pre- and posttreatment Pouchitis Disease Activity Index symptom scores (range: 0-6), endoscopic stricture scores based on resistance in passing the endoscope (range: 0-4), and Cleveland Global Quality of Life were compared. RESULTS: Nineteen patients with pouch strictures who had concurrent Crohn's disease of the pouch (n = 11), cuffitis (n = 5), and pouchitis (n = 3), including 14 inlet and 14 outlet strictures, were enrolled. The mean number of strictures for each patient was 1.61 +/- 0.78. All strictures were successfully dilated with the through-the-scope balloon, with a mean of 1.74 +/- 1.19 (range: 1-5) sessions for each patient. Nine patients had a second endoscopy at 8 wk and five patients had a third pouch endoscopy at 16 wk after the initial endoscopic dilation. Endoscopic stricture scores immediately (0.30 +/- 0.47), 8 wk (0.40 +/- 0.51), and 16 wk (0.44 +/- 0.76) after the dilation were significantly improved compared to the predilation stricture scores (2.67 +/- 0.78). The symptom scores and quality-of-life (QOL) scores improved at week 8 and 16 following dilation, with a mean follow-up of 6.10 +/- 5.83 months (2-25 months). No complications were experienced with the procedure. One patient with CD who failed endoscopic and medical therapy underwent pouch resection. CONCLUSION: In conjunction with medical therapy, outpatient endoscopic balloon dilation appears safe and effective in treating pouch inlet and outlet strictures, by relieving symptoms, restoring pouch patency, and improving QOL in the majority of patients.     

Absence of cardiac siderosis by MRI T2* despite transfusion burden,hepatic and serum iron overload in Lebanese patients with sickle cell disease

Background: The use of magnetic resonance imaging (MRI) to detect organ‐specific iron overload is becoming increasingly common. Although hepatic iron overload has been recognized in patients with sickle cell disease (SCD), cardiac iron deposition has only been examined in a few reports. Methods: This was a cross‐sectional study of 23 patients with SCD. Patient charts were reviewed and data collected for drug use, total lifetime transfusions (TLT), transfusion rate (TR), status of the spleen, and comorbid illnesses or infections. Blood samples were obtained for assessment of hemoglobin, serum ferritin, non‐transferrin‐bound iron (NTBI), and liver enzyme levels. Doppler echocardiography was performed to detect pulmonary hypertension (PHT) and assess left ventricular ejection fraction. Cardiac iron levels were measured by MRI T2*. Direct determination of liver iron concentration (LIC) was performed using R2 MRI. In this study, cardiac T2* >20 ms was considered normal. Results: The mean age was 24.4 ± 9.7 yr, with a male to female ratio of 15:8. A total of 9 (49.9%) patients were splenectomized. The mean TR was 14.1 ± 13.2 Units/yr, and the mean hemoglobin level was 9.0 g/dL. PHT was detected in 6 (27.3%) patients, but none had evidence of heart failure. The mean serum ferritin, LIC, and NTBI levels were 997.7 ng/mL, 4.6 mg Fe/g dw, and 1.1 ± 2.2, respectively. TR was a much better predictor of iron burden (LIC, ferritin, NTBI) than TLT. In fact, TR less than 10 Units/yr did not produce significant iron overload reflecting spontaneous losses as high as 0.11 mg/kg/d. None of the patients had evidence of cardiac iron overload (mean cardiac T2* = 37.3 ± 6.2 ms; range: 21.9–46.8 ms). There was also no statistically significant correlation between cardiac T2* values and any of the study variables. Conclusion: Our study demonstrates that TR is a stronger predictor of iron overload than TLT. It also confirms cardiac sparing in patients with SCD, even in subjects with significant transfusion burden, systemic and hepatic iron overload.