Removable silicon insertion stiffeners for neural probes using polyethylene glycol as a biodissolvable adhesive

Abstract not provide

HIGH-DENSITY, BIO-COMPATIBLE, AND HERMETIC ELECTRICAL FEEDTHROUGHS USING EXTRUDED METAL VIAS

Implanted medical devices such as pacemakers and neural prosthetics require that the electronic components that power these devices are protected from the harsh chemical and biological environment of the body. Typically, the electronics are hermetically sealed inside a bio-compatible package containing feedthroughs that transmit electrical signals, while being impermeable to particles or moisture. We present a novel approach for fabricating one of the highest densities of biocompatible hermetic feedthroughs in alumina (Al{sub 2}O{sub 3}). Alumina substrates with laser machined vias of 200 {micro}m pitch were conformally metallized and lithographically patterned. Hermetic electrical feedthroughs were formed by extruding metal stud-bumps partially through the vias. Hermeticity testing showed leak rates better than 9 x 10{sup -10} torr-l/s. Based on our preliminary results and process optimization, this extruded metal via approach is a high-density, low temperature, cost-effective, and robust method of miniaturizing electrical feedthroughs for a wide range of implantable bio-medical device applications

Towards an anti-fibrotic therapy for scleroderma: targeting myofibroblast differentiation and recruitment

BACKGROUND: In response to normal tissue injury, fibroblasts migrate into the wound where they synthesize and remodel new extracellular matrix. The fibroblast responsible for this process is called the myofibroblast, which expresses the highly contractile protein alpha-smooth muscle actin (alpha-SMA). In normal tissue repair, the myofibroblast disappears. Conversely, abnormal myofibroblast persistence is a key feature of fibrotic dieases, including scleroderma (systemic sclerosis, SSc). Myofibroblasts can be derived from differentiation of local resident fibroblasts or by recruitment of microvascular pericytes. CLINICAL PROBLEM ADDRESSED: Controlling myofibroblast differentiation and persistence is crucial for developing anti-fibrotic therapies targeting SSc. BASIC SCIENCE ADVANCES: Insights have been recently generated into how the proteins transforming growth factor beta (TGFbeta), endothelin-1 (ET-1), connective tissue growth factor (CCN2/CTGF) and platelet derived growth factor (PDGF) contribute to myofibroblast differentiation and pericyte recruitment in general and to the persistent myofibroblast phenotype of lesional SSc fibroblast, specifically. RELEVANCE TO CLINICAL CARE: This minireview summarizes recent findings pertinent to the origin of myofibroblasts in SSc and how this knowledge might be used to control the fibrosis in this disease. CONCLUSIONS: TGFbeta, ET-1, CCN2 and PDGF are likely to cooperate in driving tissue repair and fibrogenic responses in fibroblasts. TGFbeta, ET-1 and CCN2 appear to contribute to myofibroblast differentiation; PDGF appears to be involved with pericyte recruitment. Thus, different therapeutic strategies may exist for targeting the multisystem fibrotic disorder SSc

Severe aortic and arterial aneurysms associated with a TGFBR2 mutation.

BACKGROUND: A 24-year-old man presented with previously diagnosed Marfan\u27s syndrome. Since the age of 9 years, he had undergone eight cardiovascular procedures to treat rapidly progressive aneurysms, dissection and tortuous vascular disease involving the aortic root and arch, the thoracoabdominal aorta, and brachiocephalic, vertebral, internal thoracic and superior mesenteric arteries. Throughout this extensive series of cardiovascular surgical repairs, he recovered without stroke, paraplegia or renal impairment. INVESTIGATIONS: CT scans, arteriogram, genetic mutation screening of transforming growth factor beta receptors 1 and 2. DIAGNOSIS: Diffuse and rapidly progressing vascular disease in a patient who met the diagnostic criteria for Marfan\u27s syndrome, but was later rediagnosed with Loeys-Dietz syndrome. Genetic testing also revealed a de novo mutation in transforming growth factor beta receptor 2. MANAGEMENT: Regular cardiovascular surveillance for aneurysms and dissections, and aggressive surgical treatment of vascular disease

Chronic, multi-contact, neural interface for deep brain stimulation

Abstract not provide

First Evidence of Axial Shape Asymmetry and Configuration Coexistence in 74^{74}Zn: Suggestion for a Northern Extension of the N=40N=40 Island of Inversion

The excited states of $N=44$ $^{74}$Zn were investigated via $\gamma$-ray spectroscopy following $^{74}$Cu $\beta$ decay. By exploiting $\gamma$-$\gamma$ angular correlation analysis, the $2_2^+$, $3_1^+$, $0_2^+$ and $2_3^+$ states in $^{74}$Zn were firmly established. The $\gamma$-ray branching and $E2/M1$ mixing ratios for transitions de-exciting the $2_2^+$, $3_1^+$ and $2_3^+$ states were measured, allowing for the extraction of relative $B(E2)$ values. In particular, the $2_3^+ \to 0_2^+$ and $2_3^+ \to 4_1^+$ transitions were observed for the first time. The results show excellent agreement with new microscopic large-scale shell-model calculations, and are discussed in terms of underlying shapes, as well as the role of neutron excitations across the $N=40$ gap. Enhanced axial shape asymmetry (triaxiality) is suggested to characterize $^{74}$Zn in its ground state. Furthermore, an excited $K=0$ band with a significantly larger softness in its shape is identified. A shore of the $N=40$ ``island of inversion'' appears to manifest above $Z=26$, previously thought as its northern limit in the chart of the nuclides

Optimal phase for coronary interpretations and correlation of ejection fraction using late-diastole and end-diastole imaging in cardiac computed tomography angiography: implications for prospective triggering

A typical acquisition protocol for multi-row detector computed tomography (MDCT) angiography is to obtain all phases of the cardiac cycle, allowing calculation of ejection fraction (EF) simultaneously with plaque burden. New MDCT protocols scanner, designed to reduce radiation, use prospectively acquired ECG gated image acquisition to obtain images at certain specific phases of the cardiac cycle with least coronary artery motion. These protocols do not we allow acquisition of functional data which involves measurement of ejection fraction requiring end-systolic and end-diastolic phases. We aimed to quantitatively identify the cardiac cycle phase that produced the optimal images as well as aimed to evaluate, if obtaining only 35% (end-systole) and 75% (as a surrogate for end-diastole) would be similar to obtaining the full cardiac cycle and calculating end diastolic volumes (EDV) and EF from the 35th and 95th percentile images. 1,085 patients with no history of coronary artery disease were included; 10 images separated by 10% of R–R interval were retrospectively constructed. Images with motion in the mid portion of RCA were graded from 1 to 3; with ‘1’ being no motion, ‘2’ if 0 to <1 mm motion, and ‘3’ if there is >1 mm motion and/or non-interpretable study. In a subgroup of 216 patients with EF > 50%, we measured left ventricular (LV) volumes in the 10 phases, and used those obtained during 25, 35, 75 and 95% phase to calculate the EF for each patient. The average heart rate (HR) for our patient group was 56.5 ± 8.4 (range 33–140). The distribution of image quality at all heart rates was 958 (88.3%) in Grade 1, 113 (10.42%) in Grade 2 and 14 (1.29%) in Grade 3 images. The area under the curve for optimum image quality (Grade 1 or 2) in patients with HR > 60 bpm for phase 75% was 0.77 ± 0.04 [95% CI: 0.61–0.87], while for similar heart rates the area under the curve for phases 75 + 65 + 55 + 45% combined was 0.92 ± 0.02. LV volume at 75% phase was strongly correlated with EDV (LV volume at 95% phase) (r = 0.970, P < 0.001). There was also a strong correlation between LVEF (75_35) and LVEF (95_35) (r = 0.93, P < 0.001). Subsequently, we developed a formula to correct for the decrement in LVEF using 35–75% phase: LVEF (95_35) = 0.783 × LVEF (75_35) + 20.68; adjusted R2 = 0.874, P < 0.001. Using 64 MDCT scanners, in order to acquire >90% interpretable studies, if HR < 60 bpm 75% phase of RR interval provides optimal images; while for HR > 60 analysis of images in 4 phases (75, 35, 45 and 55%) is needed. Our data demonstrates that LVEF can be predicted with reasonable accuracy by using data acquired in phases 35 and 75% of the R–R interval. Future prospective acquisition that obtains two phases (35 and 75%) will allow for motion free images of the coronary arteries and EF estimates in over 90% of patients

CCN2 Is Required for the TGF-β Induced Activation of Smad1 - Erk1/2 Signaling Network

Connective tissue growth factor (CCN2) is a multifunctional matricellular protein, which is frequently overexpressed during organ fibrosis. CCN2 is a mediator of the pro-fibrotic effects of TGF-β in cultured cells, but the specific function of CCN2 in the fibrotic process has not been elucidated. In this study we characterized the CCN2-dependent signaling pathways that are required for the TGF-β induced fibrogenic response. By depleting endogenous CCN2 we show that CCN2 is indispensable for the TGF-β-induced phosphorylation of Smad1 and Erk1/2, but it is unnecessary for the activation of Smad3. TGF-β stimulation triggered formation of the CCN2/β3 integrin protein complexes and activation of Src signaling. Furthermore, we demonstrated that signaling through the αvβ3 integrin receptor and Src was required for the TGF-β induced Smad1 phosphorylation. Recombinant CCN2 activated Src and Erk1/2 signaling, and induced phosphorylation of Fli1, but was unable to stimulate Smad1 or Smad3 phosphorylation. Additional experiments were performed to investigate the role of CCN2 in collagen production. Consistent with the previous studies, blockade of CCN2 abrogated TGF-β-induced collagen mRNA and protein levels. Recombinant CCN2 potently stimulated collagen mRNA levels and upregulated activity of the COL1A2 promoter, however CCN2 was a weak inducer of collagen protein levels. CCN2 stimulation of collagen was dose-dependent with the lower doses (<50 ng/ml) having a stimulatory effect and higher doses having an inhibitory effect on collagen gene expression. In conclusion, our study defines a novel CCN2/αvβ3 integrin/Src/Smad1 axis that contributes to the pro-fibrotic TGF-β signaling and suggests that blockade of this pathway may be beneficial for the treatment of fibrosis