Stable polymer brushes with effectively varied grafting density synthesized from highly crosslinked random copolymer thin films

We demonstrate the synthesis of poly(methyl methacrylate) (PMMA) and poly(styrene-b-methyl methacrylate) (P(S-b-MMA)) brushes on crosslinked random copolymer thin films, compositionally varied poly(styrene-r-glycidyl methacrylate) (P(S-r-GMA)), which can be further functionalized with a molecule featuring an initiator group upon crosslinking to form highly stable thin films. With careful optimizations, PMMA brushes were successfully grown from the surfaces of initiator functionalized P(S-r-GMA) via surface-initiated atom transfer radical polymerization. The grafting densities of the PMMA and P(S-b-MMA) brushes were effectively controlled to be in different density regimes by controlling the composition of P(S-r-GMA) and post-crosslinking functionalization methods. Synthesized BCP brushes were stable upon repetitive washing and thermal annealing processes even at high grafting density, highlighting that the outstanding stability of crosslinked P(S-r-GMA) thin films enables close examination of the morphology of thermally annealed P(S-b-MMA) brushes in different grafting density regimes.

Crosslinkable epoxy copolymers enable achieving highly stable P(S-b-MMA) brushes with controlled grafting density for close examination of phase separation behaviors.     

Seasonal Patterns of Buruli Ulcer Incidence,Central Africa, 2002–2012

To determine when risk for Buruli ulcer is highest, we examined seasonal patterns in a highly disease-endemic area of Cameroon during 2002–2012. Cases peaked in March, suggesting that risk is highest during the high rainy season. During and after this season, populations should increase protective behaviors, and case detection efforts should be intensified.     

Cardioprotective Efficacy of Verapamil and Mibefradil in Young UM-X7.1 Cardiomyopathic Hamsters

Summary. Since calcium overload and increased in T-type calcium channel activity have been observed in the cardiomyopathic (CM) hamster, we hypothesized that mibefradil (Ro 40-5967), a new T- and L-type calcium channel blocker, may exert significant cardioprotection in the early phase of the disease. Young (30-day-old) CM hamsters of the UM-X7.1 subline were treated with mibefradil or verapamil for 4 to 6 weeks. Mibefradil doses were in the range of 0.5 to 8 mg/kg/day while verapamil was given at a dose of 5–10 mg/kg/day, both drugs being injected twice daily (sc and ip alternatively). At the end of the treatment period, myocardial and skeletal muscle (tongue) were harvested and processed for assessment of necrotic changes and calcification. In hearts from control CM hamsters, numerous necrotic and calcified foci were observed. These myocardial necrosis markers were not attenuated by mibefradil in the dose range studied whereas verapamil significantly reduced their severity. The dystrophic process in skeletal muscle (tongue) was not inhibited by mibefradil or verapamil. These results suggest that mechanisms other than inhibition of T- and L-type calcium channels are related to the cardioprotection observed in the presence of verapamil. A specific action on the sarcoplasmic reticulum (ryanodine-sensitive calcium channel) or the mitochondria may explain the efficacy of phenylalkylamines (verapamil) in this condition.     

Increased expression of connective tissue growth factor in fibrotic human liver and in activated hepatic stellate cells

BACKGROUND/AIMS: Connective tissue growth factor is a recently described mitogenic protein implicated in a variety of fibrotic disorders. Connective tissue growth factor may be a downstream mediator of the pro-fibrotic and mitogenic actions of transforming growth factor-beta, promoting extracellular matrix deposition and fibrogenesis. As transforming growth factor-beta is considered important to the pathogenesis of hepatic fibrosis, we examined the possible contribution of connective tissue growth factor to this process. METHODS: Connective tissue growth factor expression was examined in normal and fibrotic human and rat livers using RT-PCR and ribonuclease protection assays, and in primary cultures of rat hepatic stellate cells by Northern and Western blotting. RESULTS: Ribonuclease protection assays demonstrated connective tissue growth factor mRNA was increased 3-5-fold in human fibrotic liver compared with normal. RT-PCR showed this mRNA was increased in carbon-tetrachloride-treated rat liver. Northern analysis showed connective tissue growth factor mRNA was increasingly expressed during progressive activation of cultured rat hepatic stellate cells. Western analysis confirmed that freshly isolated hepatic stellate cells secreted relatively little connective tissue growth factor compared with hepatic stellate cells activated in culture. Hepatic stellate cells stimulated with transforming growth factor-beta showed increased expression of connective tissue growth factor mRNA and protein. CONCLUSIONS: Connective tissue growth factor mRNA is consistently upregulated in human liver cirrhosis of various aetiologies, supporting a role for this growth factor in hepatic fibrogenesis. Our studies suggest that hepatic stellate cells may be an important source of hepatic connective tissue growth factor in vivo, particularly following stimulation with transforming growth factor-beta.     

Nocturnal pain correlates with effusions in diseased hips.

Thirty-five of 50 patients with different hip joint disease had sonographic evidence of joint effusion. Arthrocentesis confirmed effusions in 30 of these 35 patients. Thirty-two of the 35 patients had nocturnal pain. Both nocturnal pain and sonographic evidence of effusion decreased after aspiration (15 patients) and aspiration and injection of corticosteroids (15 patients). In a further group of 61 patients who subsequently had Charnley arthroplasties, 35 had positive sonograms before operation. Of these, 25 had effusions confirmed at operation, the remaining 10 having synovitis and capsule thickening. Again a correlation was found with nocturnal pain. The sensitivity of sonography in detecting hip joint effusion was 92% with a specificity of 70%. Nocturnal pain had a lower sensitivity, 85%, but higher specificity, 94%.     

Detection of multiple viral and bacterial infections in acute exacerbation of chronic obstructive pulmonary disease: A pilot prospective study

Few studies have evaluated the contribution of multiple virus and bacterial infections in acute exacerbation of chronic obstructive pulmonary disease. This study estimated the burden of multiple viral and bacterial respiratory infections in moderate to very severe chronic obstructive pulmonary disease patients that were prospectively followed‐up during a 12‐month pilot study. Clinical data were collected monthly and sputum was collected at the time of each acute exacerbation event. Classical culture techniques for bacteria and multiplex polymerase chain reaction (PCR) and microarray detection assays were performed to identify viral and atypical bacterial pathogens in the sputum. Overall, 51 patients were included and 45 acute exacerbation events were investigated clinically and microbiologically. Among the 45 acute exacerbation events, 44% had evidence of viral infection involving human rhinovirus (HRV) and metapneumovirus (hMPV) in 20% and 18%, respectively. Intracellular bacteria were not found in sputum by PCR. Common bacterial pathogens were identified in 42% of acute exacerbation patients, most frequently Branhamella catarrhalis, Streptococcus pneumoniae and Haemophilus influenzae. Viral or virus and bacteria co‐infections were detected in 27% of acute exacerbation events (n = 12) with HRV and hMPV involved in 92% of cases. Patients with co‐infections did not present greater clinical severity scores at exacerbation and more recurrence of acute exacerbation events at 3 and 6 months than those with single infections (P > 0.4). These results suggest that HRV and hMPV may be contributors or cofactors of AECOPD. These findings indicate that viral or virus and bacterial co‐infections do not impact significantly on the clinical severity of acute exacerbation of chronic obstructive pulmonary disease and recurrence at 3 and 6 months. J. Med. Virol. 85:866–873, 2013. © 2013 Wiley Periodicals, Inc.     

The Extent of Late Gadolinium Enhancement Can Predict Adverse Cardiac Outcomes in Patients with Non-Ischemic Cardiomyopathy with Reduced Left Ventricular Ejection Fraction: A Prospective Observational Study

ObjectiveThe clinical course of an individual patient with heart failure is unpredictable with left ventricle ejection fraction (LVEF) only. We aimed to evaluate the prognostic value of cardiac magnetic resonance (CMR)-derived myocardial fibrosis extent and to determine the cutoff value for event-free survival in patients with non-ischemic cardiomyopathy (NICM) who had severely reduced LVEF.Materials and MethodsOur prospective cohort study included 78 NICM patients with significantly reduced LV systolic function (LVEF < 35%). CMR images were analyzed for the presence and extent of late gadolinium enhancement (LGE). The primary outcome was major adverse cardiac events (MACEs), defined as a composite of cardiac death, heart transplantation, implantable cardioverter-defibrillator discharge for major arrhythmia, and hospitalization for congestive heart failure within 5 years after enrollment.ResultsA total of 80.8% (n = 63) of enrolled patients had LGE, with the median LVEF of 25.4% (19.8–32.4%). The extent of myocardial scarring was significantly higher in patients who experienced MACE than in those without any cardiac events (22.0 [5.5–46.1] %LV vs. 6.7 [0–17.1] %LV, respectively, p = 0.008). During follow-up, 51.4% of patients with LGE ≥ 12.0 %LV experienced MACE, along with 20.9% of those with LGE ≤ 12.0 %LV (log-rank p = 0.001). According to multivariate analysis, LGE extent more than 12.0 %LV was independently associated with MACE (adjusted hazard ratio, 6.71; 95% confidence interval, 2.54–17.74; p < 0.001).ConclusionIn NICM patients with significantly reduced LV systolic function, the extent of LGE is a strong predictor for long-term adverse cardiac outcomes. Event-free survival was well discriminated with an LGE cutoff value of 12.0 %LV in these patients.     

Risk Factors of Transfusion in Anemia of Very Low Birth Weight Infants

Purpose

Anemia of prematurity is frequent in preterm infants, for which red blood cell (RBC) transfusion remains the treatment of choice. In this study, we attempted to evaluate the characteristics and risk factors of anemia of prematurity, and suggest ways to reduce anemia and the need for multiple transfusions.

Materials and Methods

Preterm infants weighing less than 1500 g (May 2008-May 2009) were divided into two groups depending on whether they received RBC transfusions (transfusion group and non transfusion group). Hemoglobin (Hb) concentration, phlebotomy blood loss, and the amount of RBC transfusion were analyzed. Risk factors of anemia and RBC transfusions were analyzed.

Results

Fifty infants that survived were enrolled in the present study: 39 in the transfusion group and 11 in the non transfusion group. Hb concentrations gradually decreased by eight weeks. In the transfusion group, gestational age and birth weight were smaller, bronchopulmonary dysplasia and sepsis were more frequent, full feeding was delayed, parenteral nutrition and days spent in the hospital were prolonged, and phlebotomy blood loss was greater than that in the non transfusion group.

Conclusion

Anemia of prematurity was correlated with increased laboratory blood loss, decreased birth weight, prolonged parenteral nutrition, and delayed body weight gain. Accordingly, reducing laboratory phlebotomy loss and parenteral nutrition, as well as improving body weight gain, may be beneficial to infants with anemia of prematurity.