Imaging localized electric fields with nanometer precision through tip-enhanced Raman scattering.

Tip-enhanced Raman scattering (TERS) can be used to image plasmon-enhanced local electric field variations with extremely high spatial resolution under ambient conditions. This is illustrated through TERS images recorded using a silver atomic force microscope tip coated with strategically selected molecular reporters and used to image a sputtered silver film.

Visualizing surface plasmons with photons, photoelectrons, and electrons.

Both photons and electrons may be used to excite surface plasmon polaritons, the collective charge density fluctuations at the surface of metal nanostructures. By virtue of their nanoscopic and dissipative nature, a detailed characterization of surface plasmon (SP) eigenmodes in real space-time ultimately requires joint nanometer spatial and femtosecond temporal resolution. The latter realization has driven significant developments in the past few years, aimed at interrogating both localized and propagating SP modes. In this mini-review, we briefly highlight different techniques employed by our own groups to visualize the enhanced electric fields associated with SPs. Specifically, we discuss recent hyperspectral optical microscopy, tip-enhanced Raman nano-spectroscopy, nonlinear photoemission electron microscopy, as well as correlated scanning transmission electron microscopy-electron energy loss spectroscopy measurements targeting prototypical plasmonic nanostructures and constructs. Through selected practical examples from our own laboratories, we examine the information content in multidimensional images recorded by taking advantage of each of the aforementioned techniques. In effect, we illustrate how SPs can be visualized at the ultimate limits of space and time.

Clinical features predict responsiveness to imatinib in platelet-derived growth factor receptor-alpha-negative hypereosinophilic syndrome.

BACKGROUND: With the exception of the presence of the FIP1L1-PDGFRA fusion gene, little is known about predictors of imatinib response in clinically-defined hypereosinophilic syndrome (HES). METHODS: Subjects with FIP1L1-PDGFRA-myeloid neoplasm (FP; n =12), PDGFRA-negative HES with ≥4 criteria suggestive of a myeloid neoplasm (MHES; n =10), or steroid-refractory PDGFRA-negative HES with <4 myeloid criteria (SR; n = 5) were enrolled in a prospective study of imatinib therapy (NCT00044304: registered at clinicaltrials.gov). The primary outcome was an eosinophil count <1.5 × 109/L at one month and improvement of clinical symptoms. Clinical, molecular, and bone marrow responses to imatinib were assessed. A retrospective cohort of 18 subjects with clinically-defined HES who received imatinib (300-400 mg daily ≥ 1 month) were classified according to the criteria used in the prospective study. RESULTS: Overall, imatinib response rates were 100% in the FP group (n = 16), 54% in the MHES group (n = 13) and 0% in the SR group (n = 16). The presence of ≥ 4 myeloid features was the sole predictor of response. After ≥ 18 months in complete remission, imatinib was tapered and discontinued in 8 FP and 1 MHES subjects. Seven subjects (6 FP, 1 MHES) remain in remission off therapy for a median of 29 months (range 14-36). CONCLUSIONS: Clinical features of MHES predict imatinib response in PDGFRA-negative HES.

Global sampling of the photochemical reaction paths of bromoform by ultrafast deep-UV through near-IR transient absorption and ab initio multiconfigurational calculations.

Ultrafast deep-ultraviolet through near infrared (210-950 nm) transient absorption spectroscopy complemented by ab initio multiconfigurational calculations offers a global description of the photochemical reaction pathways of bromoform following 255-nm excitation in methylcyclohexane and acetonitrile solutions. Photoexcitation of CHBr3 leads to the ground-state iso-CHBr3 product in a large quantum yield (∼35%), formed through two different mechanisms: concerted excited-state isomerization and cage-induced isomerization through the recombination of the nascent radical pair. These two processes take place on different time scales of tens of femtoseconds and several picoseconds, respectively. The novel ultrafast direct isomerization pathway proposed herein is consistent with the occurrence of a conical intersection between the first excited singlet state of CHBr3 and the ground electronic state of iso-CHBr3. Complete active space self-consistent field calculations characterize this singularity in the vicinity of a second order saddle point on the ground state which connects the two isomer forms. For cage-induced isomerization, both the formation of the nascent radical pair and its subsequent collapse into ground-state iso-CHBr3 are directly monitored through the deep-ultraviolet absorption signatures of the radical species. In both mechanisms, the optically active (i.e., those with largest Franck-Condon factors) C-Br-Br bending and Br-Br stretching modes of ground-state iso-CHBr3 have the largest projection on the reaction coordinate, enabling us to trace the structural changes accompanying vibrational relaxation of the non-equilibrated isomers through transient absorption dynamics. The iso-CHBr3 photoproduct is stable in methylcyclohexane, but undergoes either facile thermal isomerization to the parent CHBr3 structure through a cyclic transition state stabilized by the polar acetonitrile medium (∼300-ps lifetime), and hydrolysis in the presence of water.

Subsurface synthesis and characterization of Ag nanoparticles embedded in MgO.

Metal nanoparticles exhibit a localized surface plasmon resonance (LSPR) which is very sensitive to the size and shape of the nanoparticle and the surrounding dielectric medium. The coupling between the electromagnetic radiation and the localized surface plasmon in metallic nanoparticles results in a sizable enhancement of the incident fields, making them possible candidates for plasmonic applications. In particular, partially exposed metallic nanoparticles distributed in a dielectric matrix can provide prime locations for LSPR spectroscopy and sensing. We report the synthesis and characterization of a plasmonic substrate consisting of Ag nanoparticles partially buried in MgO. Ag nanoparticles of different shapes and size distributions were synthesized below the surface of MgO by implanting 200 keV Ag(+) ions followed by annealing at 1000 °C for 10 and 30 h. A detailed optical and structural characterization was carried out to understand the evolution of the Ag nanoparticle and size distribution inside the MgO matrix. Micro x-ray diffraction (Micro-XRD) was employed to investigate the structural properties and estimate the crystallite size. The nanoparticles evolved from a spherical to a faceted morphology with annealing time, assuming an octahedral shape truncated at the (001) planes, as visualized from aberration-corrected transmission electron microscopy (TEM) images. The nanoparticles embedded in MgO were shown to be pure metallic Ag using atom probe tomography (APT). The nanoparticles were partially exposed to the surface by employing plasma etch techniques to remove the overlaying MgO. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were employed to study the surface morphology and obtain a height distribution for the partially exposed nanoparticles.

Patterns of pain across the acute SCI rehabilitation stay: evidence from hourly ratings.

STUDY DESIGN: Cohort. OBJECTIVES: To examine patterns of pain intensity and variability during acute spinal cord injury (SCI) rehabilitation. SETTING: Large medical university in the Midwestern United States. METHODS: Data were collected from the medical records of consecutively admitted patients with new (< or =2 months after onset), traumatic (that is, injury resulting from external forces) or non-traumatic (that is, injury resulting from disease processes) SCI. A total of 11,001 hourly pain ratings on 1709 inpatient days were collected from 56 inpatients. Multi-leveling modeling was used to test models of pain intensity, pain variability, diurnal variability and pain medication administration. RESULTS: Pain intensity and variability decreased during the inpatient stay. Compared with those with non-traumatic injuries, those with traumatic injuries had significantly higher pain; those with American Spinal Injury Association Impairment Score (AIS) A scores had a slower decline of pain, while those with AIS D scores had a sharper decline. Pain increased from morning to evening during the latter days of the inpatient stay whereas pain was relatively stable during the early days in the inpatient stay. Those not using a ventilator at admission were significantly less likely to receive a pain medication than those who were, despite no significant differences in pain levels. CONCLUSION: Pain changes during acute rehabilitation, however, the moderating effect of time suggests that change is not consistent across all injury characteristics. Findings suggest that not only should pain management be individualized but it should also reflect a greater understanding of change over time.

Serum biomarkers are similar in Churg-Strauss syndrome and hypereosinophilic syndrome.

RATIONALE: Churg-Strauss syndrome (CSS) and hypereosinophilic syndrome (HES) overlap considerably in clinical presentation. A reliable means of distinguishing between these groups of patients is needed, especially in the setting of glucocorticoid therapy. METHODS: A retrospective chart review of 276 adult subjects referred for evaluation of eosinophilia > 1500/µl was performed, and subjects with a documented secondary cause of eosinophilia or a PDGFR -positive myeloproliferative neoplasm were excluded. The remaining subjects were assessed for the presence of American College of Rheumatology (ACR) criteria. Laboratory and clinical parameters were compared between subjects with biopsy-proven vasculitis (CSS; n = 8), ≥4 ACR criteria (probable CSS; n = 21), HES with asthma and/or sinusitis without other CSS-defining criteria (HESwAS; n = 20), HES without asthma or sinusitis (HES; n = 18), and normal controls (n = 8). Serum biomarkers reported to be associated with CSS were measured using standard techniques. RESULTS: There were no differences between the subjects with definite or probable CSS or HES with respect to age, gender, or maintenance steroid dose. Serum CCL17, IL-8, and eotaxin levels were significantly increased in eosinophilic subjects as compared to normal controls, but were similar between the eosinophilic groups. Serum CCL17 correlated with eosinophil count (P < 0.0001, r = 0.73), but not with prednisone dose. CONCLUSIONS: In patients with a history of asthma and sinusitis, distinguishing between ANCA-negative CSS and PDGFR-negative HES is difficult because of significant overlap in clinical presentation and biomarker profiles.

Insulin resistance and arterial stiffness in healthy adolescents and young adults.

AIMS/HYPOTHESIS: Increased arterial stiffness is a risk factor for adverse cardiovascular events in adults with obesity-related insulin resistance (IR) or type 2 diabetes mellitus. Adolescents with type 2 diabetes have stiffer vessels. Whether stiffness is increased in obesity/IR in youth is not known. We sought to determine if IR was a determinant of arterial stiffness in youth, independent of obesity and cardiovascular risk factors. METHODS: We measured cardiovascular risk factors, IR, adipocytokines and arterial stiffness (brachial artery distensibility [BrachD], pulse wave velocity [PWV]) and wave reflection (augmentation index [AIx]) in 343 adolescents and young adults without type 2 diabetes (15-28 years old, 47% male, 48% non-white). Individuals <85th percentile of BMI were classified as lean (n = 232). Obese individuals were grouped by HOMA index as not insulin resistant (n = 46) or insulin resistant (n = 65) by the 90th percentile for HOMA for lean. Mean differences were evaluated by ANOVA. Multivariate models evaluated whether HOMA was an independent determinant of arterial stiffness. RESULTS: Risk factors deteriorated from lean to obese to obese/insulin resistant (all p ≤ 0.017). Higher AIx, lower BrachD and higher PWV indicated increased arterial stiffness in obese and obese/insulin-resistant participants. HOMA was not an independent determinant. Age, sex, BMI and BP were the most consistent determinants, with HDL-cholesterol playing a role for BrachD and leptin for PWV (AIx R²= 0.34; BrachD R² = 0.37; PWV R² = 0.40; all p ≤ 0.02). CONCLUSIONS/INTERPRETATION: Although IR is associated with increased arterial stiffness, traditional cardiovascular risk factors, especially obesity and BP, are the major determinants of arterial stiffness in healthy young people.

The effects of obesity and type 2 diabetes mellitus on cardiac structure and function in adolescents and young adults.

AIMS/HYPOTHESIS: We sought to evaluate the effects of obesity and obesity-related type 2 diabetes mellitus on cardiac geometry (remodelling) and systolic and diastolic function in adolescents and young adults. METHODS: Cardiac structure and function were compared by echocardiography in participants who were lean, obese or obese with type 2 diabetes (obese diabetic), in a cross sectional study. Group differences were assessed using ANOVA. Independent determinants of cardiac outcome measures were evaluated with general linear models. RESULTS: Adolescents with obesity and obesity-related type 2 diabetes were found to have abnormal cardiac geometry compared with lean controls (16% and 20% vs <1%, p < 0.05). These two groups also had increased systolic function. Diastolic function decreased from the lean to obese to obese diabetic groups with the lowest diastolic function observed in the obese diabetic group (p < 0.05). Regression analysis showed that group, BMI z score (BMIz), group × BMIz interaction and systolic BP z score (BPz) were significant determinants of cardiac structure, while group, BMIz, systolic BPz, age and fasting glucose were significant determinants of the diastolic function (all p < 0.05). CONCLUSIONS/INTERPRETATION: Adolescents with obesity and obesity-related type 2 diabetes demonstrate changes in cardiac geometry consistent with cardiac remodelling. These two groups also demonstrate decreased diastolic function compared with lean controls, with the greatest decrease observed in those with type 2 diabetes. Adults with diastolic dysfunction are known to be at increased risk of progressing to heart failure. Therefore, our findings suggest that adolescents with obesity-related type 2 diabetes may be at increased risk of progressing to early heart failure compared with their obese and lean counterparts.

Spectroscopic and computational studies of the laser photolysis of matrix isolated 1,2-dibromoethanes: formation and fate of the bromoethyl radicals.

We report experimental and computational studies of the photolysis of atmospherically important 1,2-dibromoethanes (1,2-C(2)X(4)Br(2); X = H, F) in Ar matrixes at 5 K. Using the pulsed deposition method, we find that significant conformational relaxation occurs for 1,2-C(2)H(4)Br(2) (EDB; observed anti/gauche ratio =30:1) but not for 1,2-C(2)F(4)Br(2) (TFEDB; anti/gauche = 3:1), which is traced to a larger barrier to rotation about the C-C bond in the latter. Laser photolysis of matrix-isolated EDB at 220 nm reveals the growth of infrared bands assigned to the gauche conformer and C(2)H(4)-Br(2) charge transfer complex (both as major products), and the C(2)H(4)Br radical and C(2)H(3)Br-HBr complex as minor (trace) products. The presence of the C(2)H(4)-Br(2) complex is confirmed in the UV/visible spectrum, which shows an intense charge transfer band at 237 nm that grows in intensity upon annealing. In contrast to previous reports, our experimental and computational results do not support a bridged structure for the C(2)H(4)Br radical in either the gas phase or matrix environments. We also report on the laser photolysis of matrix-isolated TFEDB at 220 nm. Here, the dominant photoproducts are the anti and gauche conformers of the C(2)F(4)Br radical, the vibrational and electronic spectra of which are characterized here for the first time. The increase in yield of radical for TFEDB vs EDB is consistent with the stronger C-Br bond in the fluoro-substituted radical species. The photochemistry of the C(2)F(4)Br radical following excitation at 266 nm was investigated and found to lead C-Br bond cleavage and formation of C(2)F(4). The implications of this work for the atmospheric and condensed phase photochemistry of the alkyl halides is emphasized.

Gender differences in the relationships among obesity, adiponectin and brachial artery distensibility in adolescents and young adults.

BACKGROUND: Obesity-related cardiovascular diseases (CVDs) are a major cause of cardiovascular (CV) mortality. Obesity-related reduction in vascular protective adipose-derived proteins, such as adiponectin (APN), has an important role. METHODS: We compared brachial artery distensibility (BrachD) with APN, the level of adiposity and other CV risk factors (CVRFs) in 431 post-pubertal subjects (mean 17.9 years). Gender differences in average values were examined by t-tests. Correlations among BrachD, obesity and other CVRFs were examined. Regression analysis was performed to determine whether APN provided an independent contribution to BrachD, while controlling for obesity and other CVRFs. RESULTS: Male subjects had lower BrachD (5.72+/-1.37 vs 6.45+/-1.60% change per mm Hg, P<0.0001) and lower APN (10.50+/-4.65 vs 13.20+/-6.53; all P<0.04) than female subjects. BrachD correlated with APN (r=0.25, P< 0.0001). Both BrachD and APN correlated with measures of body size, including height, weight and body mass index (BMI). Both correlated with higher systolic blood pressure, glucose, insulin and lower high-density lipoprotein cholesterol (all P<0.01). In multivariate analysis, APN, gender, APN*gender and BMI z-score predicted BrachD (r(2)=0.305). On the basis of gender difference, only BMI z-score was significant for male subjects (r(2)=0.080), whereas APN and BMI z-score contributed for female subjects (r(2)=0.242, all P<0.0001). CONCLUSIONS: BrachD is independently influenced by obesity in both male and female subjects. In female subjects, APN exerts an additional independent effect even after adjusting for blood pressure (BP), lipid levels and insulin. Differences in the effect of the APN-adiposity relationship on obesity-related vascular disease may be one reason for gender differences in the development and progression of atherosclerosis.

Acquired renal cysts after pediatric liver transplantation: association with cyclosporine and renal dysfunction.

ACKD has been observed in children on dialysis and with chronic renal insufficiency. In one report, ACKD was observed in 30% of pediatric liver transplant recipients after 10 yr. We retrospectively reviewed all renal imaging and measurements of GFR of 235 childhood liver transplant recipients with no known risk for renal cyst formation, no evidence of renal cyst(s) at the time of transplantation and renal imaging at least one yr post-transplant. Twenty-six patients (11%) developed one or more cyst(s). Mean GFR was significantly lower in patients with renal cyst(s). Two (1.4%) of the 146 patients treated with tacrolimus and 24 (27%) of the 89 patients treated with CsA acquired renal cyst(s) (p < 0.001). CsA-treated patients had significantly lower GFR. Multivariate analysis identified CsA as the only independent variable associated with ACKD. These results confirm that ACKD can be a late complication of pediatric liver transplantation. Those at most risk are at least 10-yr post-liver transplantation, have been treated with CsA and have impaired renal function. We speculate that ACKD in these patients is the result of calcineurin inhibitor nephrotoxicity. Whether patients with ACKD will be prone to develop solid renal tumors is unknown.

Early manifestations and spectrum of recipient twin cardiomyopathy in twin-twin transfusion syndrome: relation to Quintero stage.

OBJECTIVES: To examine cardiac structural and functional changes in twin-twin transfusion syndrome (TTTS), relative to Quintero stage, as a means of evaluating the spectrum of cardiomyopathy in TTTS. METHODS: This was a cross-sectional, retrospective study of 42 consecutive cases of TTTS referred to a single fetal therapy center. Quintero stages were assigned by standard criteria. Presence of ventricular hypertrophy, cardiomegaly, atrioventricular valve regurgitation (AVVR), ventricular systolic dysfunction and right ventricular outflow tract obstruction on fetal echocardiography were noted. The Doppler myocardial performance index (MPI), an index of global ventricular function, was calculated for both ventricles in subjects with adequate Doppler data. We compared cardiac changes across Quintero stages. RESULTS: There was no cardiomyopathy observed in donor twins. The majority of subjects presented at Quintero Stage I (n = 14), II (n = 14) or III (n = 11), with fewer at Stages IV (n = 2) or V (n = 1). As early as Quintero Stages I and II, a significant proportion of recipient twins had ventricular hypertrophy (17/28, 61%), AVVR (6/28, 21%) or quantitative abnormalities in either right (12/24, 50%) or left (14/24, 58%) ventricular function. Increasing prevalence of biventricular systolic dysfunction and cardiomegaly accompanied advancing Quintero stage. CONCLUSIONS: Changes in cardiac structure and function not reflected in Quintero staging occur in recipient twins early in the evolution of TTTS. Incorporation of cardiac findings into assessment of TTTS severity may prove useful in stratification of risk and treatment selection.

Two-dimensional echocardiographic valve measurements in healthy children: gender-specific differences.

The goal of this study was to create nomograms of echocardiographic two-dimensional valve dimensions based on a large group of children without heart disease. Children aged 0-18 years underwent standard echocardiographic evaluation. Referring diagnoses were chest pain, heart murmur, or syncope. Only patients with a structurally normal heart and normal systolic and diastolic function were included. All four valves were measured at their maximal dimensions. A total of 748 children (314 girls and 434 boys) met the inclusion criteria. Mean values and standard deviations were calculated, and z value nomograms based on body surface area were developed. Surprisingly, the boys had larger valve dimensions at all ages. These valve dimension differences were statistically significant for three of four valves even after adjustment for the differences in body sizes. The difference may be due to higher circulating blood volume in boys compared to that in girls. Because the differences are subtle, they reach statistical significance only when evaluated in a large group of subjects. Presented normal value data will be helpful in following cardiology patients and evaluating intervention strategy in patients with valve hypoplasia.

Steroid therapy and cardiac function in Duchenne muscular dystrophy.

Duchenne muscular dystrophy leads to progressive deterioration in skeletal and cardiac muscle function. Steroids prolong ambulation and improve respiratory muscle strength. The authors hypothesized that steroid treatment would stabilize cardiac muscle function. Echocardiograms performed from 1997 to 2004 for 111 subjects 21 years of age or younger with Duchenne muscular dystrophy were restrospectively reviewed. The medical record was reviewed for steroid treatment. Untreated and steroids-treated subjects did not differ in age, height, weight, body mass index, systolic and diastolic blood pressure, or left ventricular mass. The shortening fraction was lower in the untreated group. Of those treated, 29 received prednisone and 19 received deflazacort. There was no difference in the shortening fraction between the two treated subgroups. Treated subjects not receiving steroids still had a normal shortening fraction, which was no different from the shortening fraction of those still receiving treatment. As compared with the treated subjects, the untreated subjects 10 years of age or younger were 4.4 times more likely to have a shortening fraction less than< 28% (p = 0.03), and the untreated subjects older than 10 years were 15.2 times more likely to have a shortening fraction less than< 28% (p < 0.01). This retrospective study suggests that the progressive decline in cardiac function of patients with Duchenne muscular dystrophy can be altered by steroid treatment. The effect appears to be sustained beyond the duration of treatment and independent of steroid type.

Consequences of smoking and caffeine consumption during pregnancy in women with type 1 diabetes.

OBJECTIVE: To test the hypothesis that, in women with type 1 diabetes, prenatal smoking and caffeine consumption during pregnancy are associated with an increased risk of adverse maternal and perinatal outcomes. METHODS: A secondary analysis of data on pregnant women with type 1 diabetes from an interdisciplinary program of Diabetes in Pregnancy. Women were interviewed monthly, by a trained non-medical member of the research team, using a standardized questionnaire, to ascertain daily smoking habits and caffeine consumption. RESULTS: Smoking and caffeine information were available on 191 pregnancies, 168 progressing beyond 20 weeks of gestation. Early pregnancy smoking (OR 3.3, 95% CI 1.2, 8.7) and caffeine consumption (OR 4.5, 95% CI 1.2, 16.8) were associated with increased risk of spontaneous abortion when controlling for age, years since diagnosis of diabetes, previous spontaneous abortion, nephropathy and retinopathy. Smoking throughout pregnancy was significantly associated with decreased birth weight and prolonged neonatal hospital stay. Smoking throughout pregnancy (OR 0.2, 95% 0.1, 1.0) and caffeine consumption after 20 weeks (OR 0.3, 95% CI 0.1, 1.0) were associated with reduced risk of pre-eclampsia. CONCLUSIONS: Caffeine consumption during early pregnancy, regardless of glycemic control, increases the risk of spontaneous abortion. Smoking throughout pregnancy and caffeine consumption are associated with reduced risk of pre-eclampsia.