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71.
Prabu Baskaran Rengaraj Venkatesh Seema Ramakrishnan Ravilla Duraisami Sriram Gautham Iyer R K Ramnath 《Indian journal of ophthalmology》2020,68(10):2205
The aim of this study was to describe a novel device that has been designed to facilitate anterior segment and novice surgeons to perform extraocular needle-guided haptic insertion technique (X-NIT) for scleral fixation intraocular lens surgery (SFIOL). We performed SFIOL surgery using X-NIT device in 21 eyes of 21 patients. The mean preoperative best-corrected visual acuity (BCVA) was 0.5 ± 0.2 logarithm of minimum angle of resolution (log MAR), which improved by one or more lines postoperatively in all eyes. There were no intraoperative complications. Postoperatively, we noted minimal corneal edema in one patient and dispersed vitreous hemorrhage in one patient. The sharpness and angulation of the needle and the haptic holding ability of silicone stopper were found to be satisfactory. The X-NIT device may potentially improve the safety of SFIOL procedures by minimizing intraocular maneuvers. 相似文献
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73.
Hui Li Aidong Zhang Lawrence Bone Cathy Buyea Murali Ramanathan 《The AAPS journal》2014,16(3):478-487
This study aims to develop a spatial model of bone for quantitative assessments of bone mineral density and microarchitecture. A spatially structured network model for bone microarchitecture was systematically investigated. Bone mineral-forming foci were distributed radially according to the cumulative normal distribution, and Voronoi tessellation was used to obtain edges representing bone mineral lattice. Methods to simulate X-ray images were developed. The network model recapitulated key features of real bone and contained spongy interior regions resembling trabecular bone that transitioned seamlessly to densely mineralized, compact cortical bone-like microarchitecture. Model-simulated imaging profiles were similar to patients’ X-ray images. The morphometric metrics were concordant with microcomputed tomography results for real bone. Simulations comparing normal and diseased bone of 20–30 to 70–80 year-olds demonstrated the method’s effectiveness for modeling osteoporosis. The novel spatial model may be useful for pharmacodynamic simulations of bone drugs and for modeling imaging data in clinical trials. 相似文献
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75.
Megan M. Moran-Santa Maria Aimee McRae-Clark Nathaniel L. Baker Viswanathan Ramakrishnan Kathleen T. Brady 《Psychopharmacology》2014,231(21):4157-4165
Rationale
Preclinical studies suggest that stress potentiates cue-induced cocaine seeking and that this effect is more pronounced in females. These findings have not been characterized in clinical populations.Objectives
The objectives of this study were to examine the impact a pharmacological stressor, alpha-2 adrenergic receptor antagonist yohimbine, on the subjective, endocrine, and physiologic responses to drug-paired cues cocaine-dependent men and women.Methods
In a double-blind placebo-controlled cross-over study, cocaine-dependent men (n?=?32), cocaine-dependent women (n?=?30), control men (n?=?32), and control women (n?=?25) received either yohimbine or placebo prior to two cocaine cue exposure sessions.Results
Yohimbine increased ratings of anxiety both before (p?0.001) and after (p?=?0.035) cues, and the post-cue increase in anxiety was more pronounced in women (p?=?0.001). Yohimbine also significantly increased craving, compared with placebo (p?0.05), following the cue presentation, and this effect was greater in women than men (gender by treatment interaction; p?=?0.006). Yohimbine also increased salivary cortisol (p?0.001) and dehydroepiandrosterone (p?=?0.003) levels, regardless of diagnostic group. Women had a significantly greater heart rate response following yohimbine as compared with men (p?0.001).Conclusions
Stress may increase the salience of cocaine cues for cocaine-dependent women as compared with men. This suggests gender differences in vulnerability to craving and relapse under stressful conditions. 相似文献76.
77.
Balakrishnan V Unnikrishnan AG Thomas V Choudhuri G Veeraraju P Singh SP Garg P Pai CG Devi RN Bhasin D Jayanthi V Premalatha N Chacko A Kar P Rai RR Rajan R Subhalal N Mehta R Mishra SP Dwivedi M Vinayakumar KR Jain AK Biswas K Mathai S Varghese J Ramesh H Alexander T Philip J Raj VV Vinodkumar A Mukevar S Sawant P Nair P Kumar H Sudhindran S Dhar P Sudheer OV Sundaram KR Tantri BV Singh D Nath TR 《JOP : Journal of the pancreas》2008,9(5):593-600
78.
Andre Berndt Soo Yeun Lee Jonas Wietek Charu Ramakrishnan Elizabeth E. Steinberg Asim J. Rashid Hoseok Kim Sungmo Park Adam Santoro Paul W. Frankland Shrivats M. Iyer Sally Pak Sofie ?hrlund-Richter Scott L. Delp Robert C. Malenka Sheena A. Josselyn Marie Carlén Peter Hegemann Karl Deisseroth 《Proceedings of the National Academy of Sciences of the United States of America》2016,113(4):822-829
The structure-guided design of chloride-conducting channelrhodopsins has illuminated mechanisms underlying ion selectivity of this remarkable family of light-activated ion channels. The first generation of chloride-conducting channelrhodopsins, guided in part by development of a structure-informed electrostatic model for pore selectivity, included both the introduction of amino acids with positively charged side chains into the ion conduction pathway and the removal of residues hypothesized to support negatively charged binding sites for cations. Engineered channels indeed became chloride selective, reversing near −65 mV and enabling a new kind of optogenetic inhibition; however, these first-generation chloride-conducting channels displayed small photocurrents and were not tested for optogenetic inhibition of behavior. Here we report the validation and further development of the channelrhodopsin pore model via crystal structure-guided engineering of next-generation light-activated chloride channels (iC++) and a bistable variant (SwiChR++) with net photocurrents increased more than 15-fold under physiological conditions, reversal potential further decreased by another ∼15 mV, inhibition of spiking faithfully tracking chloride gradients and intrinsic cell properties, strong expression in vivo, and the initial microbial opsin channel-inhibitor–based control of freely moving behavior. We further show that inhibition by light-gated chloride channels is mediated mainly by shunting effects, which exert optogenetic control much more efficiently than the hyperpolarization induced by light-activated chloride pumps. The design and functional features of these next-generation chloride-conducting channelrhodopsins provide both chronic and acute timescale tools for reversible optogenetic inhibition, confirm fundamental predictions of the ion selectivity model, and further elucidate electrostatic and steric structure–function relationships of the light-gated pore.Discovery and engineering of the microbial opsin genes not only has stimulated basic science investigation into the structure–function relationships of proteins involved in light-triggered ion flow but also has opened up opportunities for biological investigation (reviewed in ref. 1) via the technique of optogenetics, which involves targeting these genes and corresponding optical stimuli to control activity within specified types of cells within intact and functioning biological systems. For example, optogenetics has been used to identify causally the brain cells and projections involved in behaviors relevant to memory formation, affective states, and motor function, among many other discoveries (2–4). For the channelrhodopsins, an important member of this protein family widely used in optogenetics (5, 6), the light-activated cation-conducting channel pore has been the subject of structural investigation, both because of curiosity regarding the physical properties of its ion conduction and because the creation of inhibitory channels had been sought for optogenetic applications. Converging lines of work recently achieved the latter goal; resolving the high-resolution structure of channelrhodopsin (7) allowed a principled structure-guided approach to engineering for chloride selectivity by testing an electrostatic model for pore function (8, 9). Subsequently, by screening the genome of the Guillardia theta microbe, two naturally occurring light-gated chloride-conducting channelrhodopsins (10) were identified.Because optogenetic control of behavior has not yet been demonstrated with chloride channelrhodopsins, and to test further integrative ideas regarding pore function from structural considerations as shown here, we sought to design and test the next generation of enhanced chloride channels (iC++ and SwiChR++). Along the way, we provide the initial test of the hypothesis that light-activated channels will be more efficient tools than pumps for optogenetic neuronal inhibition at the cellular level, demonstrate the initial utility of light-gated chloride channels in controlling behavior in freely moving animals, and reveal key principles regarding the functional selectivity of light-gated ion channel pores. 相似文献
79.
80.
Milton Packer William T Abraham Mandeep R Mehra Clyde W Yancy Christine E Lawless Judith E Mitchell Frank W Smart Rachel Bijou Christopher M O'Connor Barry M Massie Ileana L Pina Barry H Greenberg James B Young Daniel P Fishbein Paul J Hauptman Robert C Bourge John E Strobeck Srinvivas Murali Douglas Schocken John R Teerlink Wayne C Levy Robin J Trupp Marc A Silver 《Journal of the American College of Cardiology》2006,47(11):2245-2252
OBJECTIVES: This study sought to assess the potential utility of impedance cardiography (ICG) in predicting clinical deterioration in ambulatory patients with heart failure (HF). BACKGROUND: Impedance cardiography uses changes in thoracic electrical impedance to estimate hemodynamic variables, but its ability to predict clinical events has not been evaluated. METHODS: We prospectively evaluated 212 stable patients with HF and a recent episode of clinical decompensation who underwent serial clinical evaluation and blinded ICG testing every 2 weeks for 26 weeks and were followed up for the occurrence of death or worsening HF requiring hospitalization or emergent care. RESULTS: During the study, 59 patients experienced 104 episodes of decompensated HF (16 deaths, 78 hospitalizations, and 10 emergency visits). Multivariate analysis identified 6 clinical and ICG variables that independently predicted an event within 14 days of assessment. These included three clinical variables (visual analog score, New York Heart Association functional class, and systolic blood pressure) and three ICG parameters (velocity index, thoracic fluid content index, and left ventricular ejection time). The three ICG parameters combined into a composite score was a powerful predictor of an event during the next 14 days (p = 0.0002). Visits with a high-risk composite score had 2.5 times greater likelihood and those with a low-risk score had a 70% lower likelihood of a near-term event compared with visits at intermediate risk. CONCLUSIONS: These results suggest that when performed at regular intervals in stable patients with HF with a recent episode of clinical decompensation, ICG can identify patients at increased near-term risk of recurrent decompensation. 相似文献