The ability to program highly modulated morphology upon silicon nanowires (SiNWs) has been fundamental to explore new phononic and electronic functionalities. We here exploit a nanoscale locomotion ...of metal droplets to demonstrate a large and readily controllable morphology engineering of crystalline SiNWs, from straight ones into continuous or discrete island-chains, at temperature <350 °C. This has been accomplished via a tin (Sn) droplet mediated in-plane growth where amorphous Si thin film is consumed as precursor to produce crystalline SiNWs. Thanks to a significant interface-stretching effect, a periodic Plateau-Rayleigh instability oscillation can be stimulated in the liquid Sn droplet, and the temporal oscillation of the Sn droplets is translated faithfully, via the deformable liquid/solid deposition interface, into regular spatial modulation upon the SiNWs. Combined with a unique self-alignment and positioning capability, this new strategy could enable a rational design and single-run fabrication of a wide variety of nanowire-based optoelectronic devices.
The quaternary lidocaine derivative QX-314 is now known to produce long-lasting local anesthesia despite its positive charge. However, recent research suggests that the transient receptor potential ...vanilloid receptor agonist, capsaicin, should reduce the onset and offset times, whereas the transient receptor potential vanilloid receptor antagonist, capsazepine, should delay the onset time of sensory blockade by QX-314.
Sensory blockade in the tail of the conscious mouse was investigated using QX-314 2.5% in combination with capsaicin 0.1% and/or capsazepine (50 microg/ml). After tail injection, onset and offset times of local anesthesia were measured using the hot water tail-flick latency test.
Capsaicin reduced the onset time of local anesthesia by QX-314 by more than 75% (Mann-Whitney test, P = 0.007; n = 10 per group) with no effect on the offset time of QX-314. For QX-314 without capsaicin, the onset and offset times were 23 min (interquartile range 15-30 min) and 300 min (interquartile range 285-375 min), respectively. For QX-314 with capsaicin, the onset and offset times were 4 min (interquartile range 3-8 min) and 360 min (interquartile range 285-435 min), respectively. In the antagonist study, capsazepine without added capsaicin decreased QX-314's efficacy, as 6 out of 9 mice did not develop sensory blockade after 90 min (Fisher exact test, P = 0.009).
We have confirmed in a sensory blockade model that QX-314 is a local anesthetic with a slow onset and a long duration of reversible blockade. Capsaicin, a transient receptor potential vanilloid receptor agonist, accelerated QX-314's onset kinetics, whereas capsazepine, a transient receptor potential vanilloid receptor antagonist, decreased QX-314's efficacy. These observations raise the possibility that endovanilloids may modulate cell entry of QX-314.
There are limited long-term outcome data in eculizumab-treated patients with atypical hemolytic uremic syndrome (aHUS). We report final results from the largest prospective, observational, ...multicenter study of patients with aHUS treated with eculizumab.
Patients with aHUS who participated in any of five parent eculizumab trials and received at least one eculizumab infusion were eligible for enrollment in a long-term follow-up study. Rates of thrombotic microangiopathy (TMA) manifestations off versus on eculizumab were evaluated. Additional endpoints included change from baseline estimated glomerular filtration rate (eGFR), long-term renal outcomes, and serious targeted treatment-emergent adverse events.
Among 93 patients (0-80 years of age), 51 (55%) remained on eculizumab and 42 (45%) discontinued; for those who discontinued, 21 (50%) reinitiated therapy. Patients who reinitiated eculizumab had similar baseline clinical characteristics to patients who remained on eculizumab, with higher likelihood of genetic/autoimmune complement abnormalities, more prior TMAs, and longer disease course versus those who did not reinitiate. Mean eGFR improved rapidly and remained stable for up to 6 years on eculizumab. In patients who discontinued, there was a trend toward decreasing renal function over time from discontinuation. Additionally, off-treatment TMA manifestation rates were higher in those aged < 18 years at diagnosis, with identified genetic/autoimmune complement abnormalities, or history of multiple TMAs prior to eculizumab initiation. The safety profile was consistent with previous studies. Three definite and one possible meningococcal infections related to eculizumab were reported and resolved with treatment. Three deaths unrelated to eculizumab were reported.
The current study confirms the efficacy and safety of eculizumab in aHUS, particularly with regard to long-term renal function and TMA events. Pediatric age at disease onset and presence of genetic or autoimmune complement abnormalities are risk factors for TMA events off treatment. Overall, patients who discontinue eculizumab may be at risk for additional TMA manifestations and renal function decreases. Discontinuation of eculizumab, with careful monitoring, is an option in select patients with consideration of patient preference, organ function normalization, and risk factors for relapse, including mutational analysis, age of onset, and history of multiple TMA episodes.
ClinicalTrials.gov NCT01522170 , January 31, 2012.
The heteroepitaxial growth of crystal silicon thin films on sapphire, usually referred to as SoS, has been a key technology for high-speed mixed-signal integrated circuits and processors. Here, we ...report a novel nanoscale SoS heteroepitaxial growth that resembles the in-plane writing of self-aligned silicon nanowires (SiNWs) on R-plane sapphire. During a low-temperature growth at <350 °C, compared to that required for conventional SoS fabrication at >900 °C, the bottom heterointerface cultivates crystalline Si pyramid seeds within the catalyst droplet, while the vertical SiNW/catalyst interface subsequently threads the seeds into continuous nanowires, producing self-oriented in-plane SiNWs that follow a set of crystallographic directions of the sapphire substrate. Despite the low-temperature fabrication process, the field effect transistors built on the SoS-SiNWs demonstrate a high on/off ratio of >5 × 104 and a peak hole mobility of >50 cm2/V·s. These results indicate the novel potential of deploying in-plane SoS nanowire channels in places that require high-performance nanoelectronics and optoelectronics with a drastically reduced thermal budget and a simplified manufacturing procedure.
This article describes the role of imaging in evaluating cervical lymphadenopathy in patients from birth to their mid-20s, illustrates imaging features of normal and abnormal lymph nodes, and ...highlights nodal imaging features and head and neck findings that assist in diagnosis.
Cervical lymph node abnormalities are commonly encountered clinically and on imaging in children and young adults. Although imaging findings can lack specificity, nodal characteristics and associated head and neck imaging findings can assist in determining the underlying cause.
We recently found that peripheral administration of the quaternary lidocaine derivative, QX-314, produces long-lasting sensory and motor blockade in animals. The goal of this study was to test ...whether intrathecal QX-314 has similar properties.
We conducted a randomized, double-controlled, blinded study with female CD-1 mice. Animals in the treatment group received lumbar intrathecal QX-314 (0.5-10 mM; volume, 2 microl; each concentration, n = 6). Normal saline and lidocaine (70 mM) served as negative and positive controls (each group, n = 12), respectively. Animals were tested for up to 3 h for lumbosacral neural blockade and observed for adverse effects.
No animal injected with saline and 11 of 12 (92%) animals injected with lidocaine displayed reversible lumbosacral motor blockade (P < 0.001). QX-314 (5 mM) produced motor blockade in four of the six (67%) and sensory blockade in five of the six animals (83%; P < 0.05 vs. saline). However, six of the six mice (100%) at 5 mM QX-314 and five of the six (83%) at 10 mM exhibited marked irritation; one of the six animals at 5 mM (17%) and two of the six at 10 mM (33%) died. We observed no neural blockade without adverse effects in any animal injected with QX-314. All animals injected with saline and 11 of the 12 (92%) animals injected with lidocaine demonstrated normal behavior.
Lumbar intrathecal QX-314 concentration-dependently produced irritation and death in mice, at lower concentrations than those associated with robust motor blockade. Although QX-314 did produce long-lasting neural blockade, these findings indicate that QX-314 is unlikely to be a suitable candidate for spinal anesthesia in humans.
Isovaline, a nonproteinogenic alpha-amino acid rarely found in the biosphere, is structurally similar to the inhibitory neurotransmitters glycine and gamma-aminobutyric acid. Because glycine(A) and ...gamma-aminobutyric acid receptor agonists are antiallodynic, we hypothesized that isovaline produces antinociception in mice.
All experiments were performed on female CD-1 mice using a blinded, randomized, and controlled design. The effects of RS-isovaline were studied on nociceptive responses to (1) formalin injection into the hindpaw; (2) glutamate injection into the hindpaw; and (3) strychnine injection either into the lumbar intrathecal space or cisterna magna. We determined the effects of IV RS-isovaline (50, 150, or 500 mg/kg; n = 10/dose) or intrathecal RS-, R-, and S-isovaline, glycine, and beta-alanine into the lumbar intrathecal space (5-microL volumes of 60, 125, 250, and 500 mM; n = 9/dose/group) on the response to formalin in the paw. The response to 20 microL intraplantar glutamate (750 mM) was compared with glutamate (750 mM) coadministered with isovaline. We also determined the response to intraplantar strychnine. Lumbar intrathecal (100 microM) or intracisternal (200 microM) injections of strychnine into the lumbar intrathecal space or the cisterna magna were used to induce allodynia as a measure of glycine inhibitory dysfunction. The effects of intrathecal or intracisternal strychnine were compared with isovaline coapplied with the strychnine (n = 8/group).
In the formalin paw test, IV isovaline did not change phase I but decreased phase II responses in a dose-dependent manner (50% effective dose = 66 mg/kg, n = 10, P < 0.01). There was no effect on rotarod performance, appearance, or behavior of the mouse, and no respiratory depression. Intrathecal isovaline, glycine, and beta-alanine attenuated phase I and II responses (P < 0.01 for each drug). In contrast to beta-alanine and glycine, isovaline at maximally effective doses did not produce scratching, biting, or agitation. Intrathecal RS- and S-isovaline attenuated phase I (P < 0.05 for each group) and RS-, R-, and S-isovaline attenuated phase II responses (P < 0.05 for each group), with no significant difference between the efficacies of R- and S-enantiomers. Localized strychnine-induced glycine inhibitory dysfunction was greatly reduced by intracisternal (P < 0.01) and intrathecal (P < 0.01) isovaline. Although intraplantar strychnine did not induce peripheral allodynia, high doses of isovaline did not block the peripheral allodynia induced by glutamate.
Isovaline reduced responses in mouse pain models without producing acute toxicity, possibly by enhancing receptor modulation of nociceptive information.
Purpose
The use of peripheral tramadol to block pain has been advocated. However, since its actions in the periphery have not been elucidated fully, we tested the hypothesis that peripheral tramadol ...blocks peripheral glutamate-induced nociceptive behaviour in mice.
Methods
First, we compared the duration of paw licking after intraplantar (ipl.) glutamate administration, with and without tramadol, using a randomized blinded controlled design. Next, we established the half maximal effective concentrations (EC
50s
) for local tramadol and reference compound lidocaine in the hot water tail-flick latency test and the glutamate-induced paw allodynia assay.
Results
Tramadol reduced glutamate-induced paw licking from 33 ± 12 sec to 4 ± 4 sec (mean ± SD;
t
test,
P
< 0.05;
n
= 6 per group). The tramadol and lidocaine EC
50
nerve conduction blocks in the tail did not differ significantly (84 ± 24 mM
vs
69 ± 5 mM, respectively). Although tramadol reduced glutamate-induced allodynia (EC
50
, 46 ± 13 mM), lidocaine was more potent (EC
50
, 13 ± 5 mM; Dixon’s up-and-down method;
P
< 0.05). Tramadol was 2.5 times as effective at blocking nerve conduction in the tail compared with allodynia in the paw.
Conclusions
Local tramadol administration blocked nociceptive behaviour in mice induced by peripheral glutamate. Compared with lidocaine, the relative potency of tramadol was lower for blocking glutamate-induced allodynia than for sensory nerve conduction blockade, suggesting the activation of a pronociceptive receptor system in the periphery.
Cerebral microbleeds (CMB) attributable to cerebral amyloid angiopathy generally occur in lobar regions, whereas those attributable to hypertensive vasculopathy are deep. Inflammation may be an ...underlying mechanism for CMB, with varying associations according to CMB location. Lipoprotein phospholipase-A2 (Lp-PLA2) is a circulating enzyme marker of vascular inflammation associated with risk of ischemic stroke and dementia. We hypothesized that higher Lp-PLA2 levels would be related to higher prevalence of CMB, with possible regional specificity.
Framingham Offspring participants aged 65 years or older with available Lp-PLA2 measures and brain magnetic resonance imaging were included. Logistic regression models were used to relate Lp-PLA2 activity and mass to presence of CMB, adjusted for age, sex, medication use (aspirin, anticoagulants, and statins), systolic blood pressure, APOE, current smoking, and diabetes.
Eight-hundred nineteen participants (mean age, 73 years; 53% women) were included; 106 (13%) had CMB, 82 (10%) were lobar, and 27 (3%) were deep. We did not observe significant associations of CMB and LpPLA2 measures in multivariable adjusted analyses. However, there was a significant interaction between APOE genotype and Lp-PLA2 activity in their relation to presence of deep CMB (P interaction=0.01). Among persons with APOE ε3/ε3, the odds ratio for deep CMB was 0.95 (confidence interval, 0.59-1.53; P=0.83), whereas among those with at least 1 ε2 or ε4 allele, odds ratio was 3.46 (confidence interval, 1.43-8.36; P=0.006).
In our community-based sample of older adults, there was no significant association of Lp-PLA2 with total or lobar CMB. The association of higher levels of Lp-PLA2 activity with deep CMB among those with at least 1 APOE ε2 or ε4 allele merits replication.
PDF
