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Objective: While performing surgical excision for breast cancer (lumpectomy), it is important to ensure a clear margin of normal tissue around the cancer to achieve complete resection. The current standard is histopathology; however, it is time-consuming and labour-intensive requiring skilled personnel., Method: We describe a Hybrid Spectral-IRDx - a combination of the previously reported Spectral-IRDx tool with multimodal ultrasound and NIR spectroscopy techniques. We show how this portable, cost-effective, minimal-contact tool could provide rapid diagnosis of cancer using formalin-fixed (FF) and deparaffinized (DP) breast biopsy tissues., Results: Using this new tool, measurements were performed on cancerous/fibroadenoma and its adjacent normal tissues from the same patients (N = 14). The acoustic attenuation coefficient (α) and reduced scattering coefficient (µ' s ) (at 850, 940, and 1060 nm) for the cancerous/fibroadenoma tissues were reported to be higher compared to adjacent normal tissues, a basis of delineation. Comparing FF cancerous and adjacent normal tissue, the difference in µ' s at 850 nm and 940 nm were statistically significant (p = 3.17e-2 and 7.94e-3 respectively). The difference in α between the cancerous and adjacent normal tissues for DP and FF tissues were also statistically significant (p = 2.85e-2 and 7.94e-3 respectively). Combining multimodal parameters α and µ' s (at 940 nm) show highest statistical significance (p = 6.72e-4) between FF cancerous/fibroadenoma and adjacent normal tissues., Conclusion: We show that Hybrid Spectral-IRDx can accurately delineate between cancerous and adjacent normal breast biopsy tissue., Significance: The results obtained establish the proof-of-principle and large-scale testing of this multimodal breast cancer diagnostic platform for core biopsy diagnosis.

Background: Empyema thoracis is defined as the presence of pus in the pleural cavity and carries significant morbidity and mortality. This study aimed to explore the demographic and clinico-radiological characteristics of patients with empyema thoracis., Material and Methods: The present study was conducted in a tertiary care teaching hospital in North India. The patients diagnosed with empyema thoracis were included in the study. Demographic, etiologic, clinical, radiographic, and outcome data were prospectively collected and analyzed., Results: The study included 48 patients. The median age of empyema thoracis patients was 37(IQR 26-45) years. Common presenting symptoms were breathlessness (n = 37,77%) and chest pain (n = 34,70%). Contrast-enhanced computed tomography (CECT) of the chest showed type III empyema in 52% (21) patients followed by type 1 and type II in 25% and 22%, respectively. CECT thorax showed the collapse of lung and consolidation in (n = 28, 70%) and (n = 24, 60%) patients, respectively. All the patients, except for one, were managed with underwater seal intercostal tube drainage (ICD) procedure for the management of empyema. The median time to remove the ICD tube among 35 patients was 14 (IQR 9-21) days. Forty patients (83.3%) responded to the treatment and were discharged. Eight patients (16.7%) deteriorated and succumbed to the disease., Conclusion: Patients of empyema thoracis required a prolonged period of chest tube drainage and carried significant morbidity and mortality., Competing Interests: Conflict of interest All authors have none to declare., (Copyright © 2021 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

The role of ultrasound in medicine and biological sciences is expanding rapidly beyond its use in conventional diagnostic imaging. Numerous studies have reported the effects of ultrasound on cellular and tissue physiology. Advances in instrumentation and electronics have enabled successful in vivo applications of therapeutic ultrasound. Despite path breaking advances in understanding the biophysical and biological mechanisms at both microscopic and macroscopic scales, there remain substantial gaps. With the progression of research in this area, it is important to take stock of the current understanding of the field and to highlight important areas for future work. We present herein key developments in the biological applications of ultrasound especially in the context of nanoparticle delivery, drug delivery, and regenerative medicine. We conclude with a brief perspective on the current promise, limitations, and future directions for interfacing ultrasound technology with biological systems, which could provide guidance for future investigations in this interdisciplinary area.

Mechanical ablation with the focused ultrasound therapy histotripsy relies on the generation and action of bubble clouds. Despite its critical role for ablation, quantitative metrics of bubble activity to gauge treatment outcomes are still lacking. Here, plane wave imaging was used to track the dissolution of bubble clouds following initiation with the histotripsy pulse. Information about the rate of change in pixel intensity was coupled with an analytic diffusion model to estimate bubble size. Accuracy of the hybrid measurement/model was assessed by comparing the predicted and measured dissolution time of the bubble cloud. Good agreement was found between predictions and measurements of bubble cloud dissolution times in agarose phantoms and murine subcutaneous SCC VII tumors. The analytic diffusion model was extended to compute the maximum bubble size as well as energy imparted to the tissue due to bubble expansion. Regions within tumors predicted to have undergone strong bubble expansion were collocated with ablation. Further, the dissolution time was found to correlate with acoustic emissions generated by the bubble cloud during histotripsy insonation. Overall, these results indicate a combination of modeling and high frame rate imaging may provide means to quantify mechanical energy imparted to the tissue due to bubble expansion for histotripsy., (Creative Commons Attribution license.)

4-Coumarate: coenzyme A ligase ( 4CL ) is a key enzyme involved in the early steps of the monolignol biosynthetic pathway. It is hypothesized to modulate S and G monolignol content in the plant. Lignin removal is imperative to the paper industry and higher S/G ratio governs better extractability of lignin and economics of the pulping process. This background prompted us to predict 3D structure of two isoforms of 4CL in Leucaena leucocephala and evaluate their substrate preferences. The 3D structure of Ll4CL1 and Ll4CL2 protein were created by homology modeling and further refined by loop refinement. Molecular docking studies suggested differential substrate preferences of both the isoforms. Ll4CL1 preferred sinapic acid (- 4.91 kcal/mole), ferulic acid (- 4.84 kcal/mole), hydroxyferulic acid (- 4.72 kcal/mole), and caffeic acid (- 4.71 kcal/mole), in their decreasing order. Similarly, Ll4CL2 preferred caffeic acid (- 6.56 kcal/mole, 4 H bonds), hydroxyferulic acid (- 6.56 kcal/mole, 3 H bonds), and ferulic acid (- 6.32 kcal/mole) and sinapic acid (- 5.00 kcal/mole) in their decreasing order. Further, active site residues were identified in both the isoforms and in silico mutation and docking analysis was performed. Our analysis suggested that ASP228, TYR262, and PRO326 for Ll4CL1 and SER165, LYS247 and PRO315 for Ll4CL2 were important for their functional activity. Based on differential substrate preferences of the two isoforms, as a first step towards genetically modified Leuaena having the desired phenotype, it can be proposed that over-expression of Ll4CL1 gene and/or down-regulation of Ll4CL2 gene could yield higher S/G ratio leading to better extractability of lignin., Competing Interests: Conflict of interestAuthors declare no potential conflict of interest. Authors also confirm that there was no research involving human participants and/or animal., (© King Abdulaziz City for Science and Technology 2020.)

Objectives: Hearing impairment and ear diseases are among the world's leading causes of years lived with disability. Ear disorders are a major health problem in developing countries like India. The present research had been planned to screen the primary school children for ear morbidity and to study the various factors associated with ear morbidities so that corrective intervention can be initiated at the earliest., Methods: A cross-sectional study was conducted among all primary school children of two schools in Aliganj, Delhi. Complete enumeration of all the school children of these two primary schools was planned for this study. Modified version of World Health Organization's (WHO's) "Ten Question Plus" screening instrument was used, followed by Otoscopy examination, in all children for confirmation of ear disease, if any. Descriptive data analysis was performed., Results: Out of the total 430 study subjects, ear morbidities were found in 198 (46.0%) study participants. Presence of ear morbidity showed significant association with overcrowding, absence of a separate kitchen, passive smoking, feeding young child in lying down position, upper respiratory tract infection (URI)˃3 episodes/year and allergy (p<0.05)., Conclusions: This study has highlighted the need to detect ear diseases at the earliest thereby avoiding complications. The health examination in the schools must include screening students for ear diseases to reduce the burden of hearing disability. Inputs from the study may be used for effective prioritization and planning for prevention and management of ear diseases at the primary school level., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Organic photodiodes (OPDs) for its interesting optoelectronic properties has the potential to be utilized with complementary metal-oxide-semiconductor (CMOS) circuit for imaging, automotive, and security based applications. To achieve such a hybrid device as an image sensor, it is imperative that the quality of the OPD remains high on the CMOS substrate and that it has a well-connected optoelectronic interface with the underneath readout integrated circuit (ROIC) for efficient photogeneration and signal readout. Here, we demonstrate seamless integration of a thermally deposited visible light sensitive small molecule OPD on a standard commercial CMOS substrate using optimized doped PCBM buffer layer. Under a standard power supply voltage of 3 V, this hybrid device shows an excellent photolinearity in the entire bias regime, a high pixel sensitivity of 2 V/Lux.sec, a dynamic range (DR) of 71 dB, and a low dark leakage current density of 1 nA/cm 2 . Moreover, the integrated OPD has a minimum bandwidth of 400 kHz. The photoresponse nonuniformity being only 1.7%, achieved under research lab conditions, strengthens the notion that this fully-CMOS compatible technology has the potential to be applied in high-performance large-scale imaging array.

We report an optoelectronic device consisting of a solution-processed indium gallium zinc oxide (IGZO) thin-film transistor and vacuum-deposited small organic molecules. Depending on the configurations of the organic materials, either bulk heterojunction or planar heterojunction (PHJ), the device assumes the functionality of either a photosensor or a photoinduced memory, respectively. Under λ = 625 nm light illumination, the photosensor shows response and recovery time of ∼50 ms, responsivity of ∼5 mA/W, sensitivity above 10 4 , and a linear response. The mechanism of the photoinduced memory is studied experimentally and verified using a device simulation. We find that the memory is due to long charge retention time at the organic PHJ interface which is stable for over 9 days. It is correlated with the low leakage current found in ordered organic junctions having low subgap tail states. The presented integration of the PHJ with the transistor constitutes a new design of write-once-read-many-times memory device that is likely to be attractive for low-cost applications.

Ultrasound has been developed as both a diagnostic tool and a potent promoter of beneficial bio-effects for the treatment of chronic bacterial infections. Bacterial infections, especially those involving biofilm on implants, indwelling catheters and heart valves, affect millions of people each year, and many deaths occur as a consequence. Exposure of microbubbles or droplets to ultrasound can directly affect bacteria and enhance the efficacy of antibiotics or other therapeutics, which we have termed sonobactericide. This review summarizes investigations that have provided evidence for ultrasound-activated microbubble or droplet treatment of bacteria and biofilm. In particular, we review the types of bacteria and therapeutics used for treatment and the in vitro and pre-clinical experimental setups employed in sonobactericide research. Mechanisms for ultrasound enhancement of sonobactericide, with a special emphasis on acoustic cavitation and radiation force, are reviewed, and the potential for clinical translation is discussed., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The global pandemic of antibiotic resistance is an ever-burgeoning public health challenge, motivating the development of adjunct bactericidal therapies. Nitric oxide (NO) is a potent bioactive gas that induces a variety of therapeutic effects, including bactericidal and biofilm dispersion properties. The short half-life, high reactivity, and rapid diffusivity of NO make therapeutic delivery challenging. The goal of this work was to characterize NO-loaded microbubbles (MB) stabilized with a lipid shell and to assess the feasibility of antibacterial therapy in vitro . MB were loaded with either NO alone (NO-MB) or with NO and octafluoropropane (NO-OFP-MB) (9:1 v/v and 1:1 v/v). The size distribution and acoustic attenuation coefficient of NO-MB and NO-OFP-MB were measured. Ultrasound-triggered release of the encapsulated gas payload was demonstrated with 3-MHz pulsed Doppler ultrasound. An amperometric microelectrode sensor was used to measure NO concentration released from the MB and compared to an NO-OFP-saturated solution. The effect of NO delivery on the viability of planktonic (free living) Staphylococcus aureus (SA) USA 300, a methicillin-resistant strain, was evaluated in a 96 well-plate format. The co-encapsulation of NO with OFP increased the total volume and attenuation coefficient of MB. The NO-OFP-MB were destroyed with a clinical ultrasound scanner with an output of 2.48 MPa peak negative pressure ( in situ MI of 1.34) but maintained their echogenicity when exposed to 0.02 MPa peak negative pressure ( in situ MI of 0.01. The NO dose in NO-MB and NO-OFP-MB was more than 2-fold higher than the NO-OFP-saturated solution. Delivery of NO-OFP-MB increased bactericidal efficacy compared to the NO-OFP-saturated solution or air and OFP-loaded MB. These results suggest that encapsulation of NO with OFP in lipid-shelled MB enhances payload delivery. Furthermore, these studies demonstrate the feasibility and limitations of NO-OFP-MB for antibacterial applications., (Copyright © 2020 Lafond, Shekhar, Panmanee, Collins, Palaniappan, McDaniel, Hassett and Holland.)

Background: Tuberculosis (TB) has been a public health menace for decades. India harbors its highest burden globally. The present study was conducted to study the epidemiological profile of patients taking treatment from a directly observed treatment short-course (DOTS) center in Delhi, India., Method: Retrospective analysis of past 1-year treatment records of a total of 227 patients undergoing treatment in DOTS since June 2014-2015 was undertaken. Socio-demographic information, data related to disease status, and HIV testing were collected and analyzed., Results: The majority of cases were new (77.1%) and pulmonary TB (69.2%). The highest disease burden was found in the 20-60 year age group (72.2%) and males (58.6%). Genitourinary TB was present only among females. None of the patients was HIV positive. A significant association was found between the age group of 20-60 years and relapse and loss to follow-up cases ( P < 0.05)., Conclusions: A higher proportion of adult males aged 20-60 years constituted the majority of patients treated in the DOTS center. Focussed interventions can be designed for this age group in future public health policies to reduce disease burden in the total population. Further research is required to be undertaken in exploring reasons for higher prevalence among males and productive age group and role of age, gender in disease causation., Competing Interests: There is no conflict of interest., (Copyright: © 2019 Journal of Family Medicine and Primary Care.)

Ultrasound-enhanced recombinant tissue plasminogen activator (rt-PA) thrombolysis is under development as an adjuvant to ischemic stroke therapy. The goal of this study was to design a pulsed ultrasound (US) exposure scheme that reduced intracranial constructive interference and tissue heating, and maintained thrombolytic efficacy relative to continuous wave (CW) insonation. Three 220 kHz US schemes were evaluated, two pulsed insonation schemes (15 cycles, 68 µs pulse duration, 33% or 62.5% duty cycle) and an intermittent CW insonation scheme (50 s active, 30 s quiescent) over a 30-min treatment period. An in silico study using a finite-difference model of transcranial US propagation was performed to estimate the intracranial acoustic field and temperature rise in the skull for each insonation scheme. In vitro measurements with flow were performed to assess thrombolysis using time-lapse microscopy. Intracranial constructive interference was not reduced with pulsed US using a pulse length of 15 cycles compared to intermittent CW US. The 33.3% duty cycle pulsed US scheme reduced heating in the temporal bone as much as 60% relative to the intermittent CW scheme. All insonation schemes promoted sustained stable cavitation in vitro and augmented thrombolysis compared to rt-PA alone (p   <  0.05). Ultraharmonic (UH) and harmonic cumulative energy over a 30 min treatment period was significantly higher (p   <  0.05) for the intermittent CW US scheme compared to either pulsed US scheme. Despite the difference in cavitation emissions, no difference was observed in the clot lysis between the three US schemes. These findings demonstrate that a 33.3% duty cycle pulsed US scheme with a 15-cycle burst can reduce bone heating and achieve equivalent thrombolytic efficacy as an intermittent CW scheme.

The development of adjuvant techniques to improve thrombolytic efficacy is important for advancing ischemic stroke therapy. We characterized octafluoropropane and recombinant tissue plasminogen activator (rt-PA)-loaded echogenic liposomes (OFP t-ELIP) using differential interference and fluorescence microscopy, attenuation spectroscopy, and electrozone sensing. The loading of rt-PA in OFP t-ELIP was assessed using spectrophotometry. Further, it was tested whether the agent shields rt-PA against degradation by plasminogen activator inhibitor-1 (PAI-1). An in vitro system was used to assess whether ultrasound (US) combined with either Definity or OFP t-ELIP enhances rt-PA thrombolysis. Human whole blood clots were mounted in a flow system and visualized using an inverted microscope. The perfusate consisted of either (1) plasma alone, (2) rt-PA, (3) OFP t-ELIP, (4) rt-PA and US, (5) OFP t-ELIP and US, (6) Definity and US, or (7) rt-PA, Definity, and US (n = 16 clots per group). An intermittent US insonation scheme was employed (220 kHz frequency, and 0.44 MPa peak-to-peak pressures) for 30 min. Microscopic imaging revealed that OFP t-ELIP included a variety of structures such as liposomes (with and without gas) and lipid-shelled microbubbles. OFP t-ELIP preserved up to 76% of rt-PA activity in the presence of PAI-1, whereas only 24% activity was preserved for unencapsulated rt-PA. The use of US with rt-PA and Definity enhanced lytic efficacy (p < 0.05) relative to rt-PA alone. US combined with OFP t-ELIP enhanced lysis over OFP t-ELIP alone (p < 0.01). These results demonstrate that ultrasound combined with Definity or OFP t-ELIP can enhance the lytic activity relative to rt-PA or OFP t-ELIP alone, respectively.

Xenon (Xe) is a bioactive gas capable of reducing and stabilizing neurologic injury in stroke. The goal of this work was to develop lipid-shelled microbubbles for xenon loading and ultrasound-triggered release. Microbubbles loaded with either xenon (Xe-MB) or xenon and octafluoropropane (Xe-OFP-MB) (9:1 v/v) were synthesized by high-shear mixing. The size distribution and the frequency-dependent attenuation coefficient of Xe-MB and Xe-OFP-MB were measured using a Coulter counter and a broadband acoustic attenuation spectroscopy system, respectively. The Xe dose was evaluated using gas chromatography/mass spectrometry. The total Xe doses in Xe-MB and Xe-OFP-MB were 113.1 ± 13.5 and 145.6 ± 25.5 μl per mg of lipid, respectively. Co-encapsulation of OFP increased the total xenon dose, attenuation coefficient, microbubble stability (in an undersaturated solution), and shelf life of the agent. Triggered release of gas payload was demonstrated with 6-MHz duplex Doppler and 220-kHz pulsed ultrasound. These results constitute the first step toward the use of lipid-shelled microbubbles for applications such as neuroprotection in stroke.

The treatment of choice for cases of corneal opacity with significant cataract is often a triple procedure. However, in certain situations the chances of graft survival are poor, for example in cases with deep vascularization, secondary glaucoma, and healed viral keratitis. Under these circumstances, performing cataract surgery only might improve the visual acuity enough to maintain the patient's day-to-day activities. Performing cataract surgery, especially phacoemulsification, in these cases is challenging. Proper case selection, choosing the right technique, and a thorough idea about the difficulties and methods of tackling such cases is paramount to achieving optimum visual outcomes. In this review, we discuss the case selection and surgical modifications of performing phacoemulsification in cases with coexisting corneal opacities., (Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Multiple Myeloma (MM) is a B-cell malignancy, which is characterized by the expansion of clonal plasma cells in the bone marrow, leading to abnormal accumulation of monoclonal antibodies in circulation. Certain circulating miRNAs are deregulated in MM and their differential expression profiles in body fluids can be quantified and used to discriminate between the premalignant and malignant stages of MM. Our study identifies protein which would show affinity for a selected panel of circulating miRNAs deregulated in MM. Human RNA binding proteins were identified based on their unique RNA binding domains and their interacting probabilities with the panel of miRNAs deregulated in MM. miR-26 was used as a negative control for interaction studies. 3-D structure of candidate proteins were determined and molecular docking was performed to confirm the results. Five RNA binding proteins TROVE2, CUGBP2, DHX8, PUM2 and DKC1 were used for molecular docking studies. DKC1 showed significant hydrogen bonding as well as remarkable binding affinity values of -17.4 kcal/mol with miR-720 (2 H-bonds), -16 kcal/mol with miR-1246 (1 H-bond) and -16.9 kcal/mol with miR-1308 (3 H-bonds). Identified protein-miRNA interaction could be used to develop an economical and reliable ELISA based methodology for improved and sensitive diagnosis of MM patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Infective endocarditis (IE) is associated with high morbidity and mortality rates. The predominant bacteria causing IE is Staphylococcus aureus (S. aureus), which can bind to existing thrombi on heart valves and generate vegetations (biofilms). In this in vitro flow study, we evaluated sonobactericide as a novel strategy to treat IE, using ultrasound and an ultrasound contrast agent with or without other therapeutics. We developed a model of IE biofilm using human whole-blood clots infected with patient-derived S. aureus (infected clots). Histology and live-cell imaging revealed a biofilm layer of fibrin-embedded living Staphylococci around a dense erythrocyte core. Infected clots were treated under flow for 30 minutes and degradation was assessed by time-lapse microscopy imaging. Treatments consisted of either continuous plasma flow alone or with different combinations of therapeutics: oxacillin (antibiotic), recombinant tissue plasminogen activator (rt-PA; thrombolytic), intermittent continuous-wave low-frequency ultrasound (120-kHz, 0.44 MPa peak-to-peak pressure), and an ultrasound contrast agent (Definity). Infected clots exposed to the combination of oxacillin, rt-PA, ultrasound, and Definity achieved 99.3 ± 1.7% loss, which was greater than the other treatment arms. Effluent size measurements suggested low likelihood of emboli formation. These results support the continued investigation of sonobactericide as a therapeutic strategy for IE.

Physical characterization of an ultrasound contrast agent (UCA) aids in its safe and effective use in diagnostic and therapeutic applications. The goal of this study was to investigate the impact of temperature on the size distribution, shell properties, and stability of Definity ® , a U.S. Food and Drug Administration-approved UCA used for left ventricular opacification. A Coulter counter was modified to enable particle size measurements at physiologic temperatures. The broadband acoustic attenuation spectrum and size distribution of Definity ® were measured at room temperature (25 °C) and physiologic temperature (37 °C) and were used to estimate the viscoelastic shell properties of the agent at both temperatures. Attenuation and size distribution was measured over time to assess the effect of temperature on the temporal stability of Definity ® . The attenuation coefficient of Definity ® at 37 °C was as much as 5 dB higher than the attenuation coefficient measured at 25 °C. However, the size distributions of Definity ® at 25 °C and 37 °C were similar. The estimated shell stiffness and viscosity decreased from 1.76 ± 0.18 N/m and 0.21 × 10 -6  ± 0.07 × 10 -6 kg/s at 25 °C to 1.01 ± 0.07 N/m and 0.04 × 10 -6  ± 0.04 × 10 -6 kg/s at 37 °C, respectively. Size-dependent differences in dissolution rates were observed within the UCA population at both 25 °C and 37 °C. Additionally, cooling the diluted UCA suspension from 37 °C to 25 °C accelerated the dissolution rate. These results indicate that although temperature affects the shell properties of Definity ® and can influence the stability of Definity ® , the size distribution of this agent is not affected by a temperature increase from 25 °C to 37 °C., (Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.)

Contrast-enhanced intra-vascular ultrasound (CE-IVUS) imaging could provide clinicians a valuable tool to assess cardiovascular risk and guide the choice of therapeutic strategies. In this technical note, we evaluated the feasibility of combining subharmonic and ultraharmonic imaging to improve the performance of CE-IVUS. Vessel phantoms perfused with phospholipid-shelled ultrasound contrast agents were visualized using subharmonic, ultraharmonic and combined CE-IVUS modes with commercial peripheral and coronary imaging catheters. Flow channels as small as 0.8 mm and 0.5 mm were imaged at 12-MHz and 30-MHz transmit frequencies, respectively. Subharmonic and ultraharmonic imaging modes achieved a contrast-to-tissue ratio (CTR) up to 18.1 ± 1.8 dB and 19.6 ± 1.9 dB at 12-MHz, and 8.8 ± 1.8 and 12.5 ± 1.1 dB at 30-MHz transmit frequencies, respectively. Combining these modes improved the CTR to 32.5 ± 3.0 dB and 25.0 ± 1.6 dB at 12-MHz and 30-MHz transmit frequencies. These results underscore the potential of combined-mode CE-IVUS imaging. Furthermore, the demonstration of this approach with commercial catheters may serve as a first step toward the clinical translation of CE-IVUS., (Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Introduction: Porcine thrombi are employed routinely in preclinical models of ischemic stroke. In this study, we examined the differential lytic susceptibility of porcine and human whole blood clots with and without the use of microbubbles and ultrasound (US) as an adjuvant., Materials and Methods: An in vitro system equipped with time-lapse microscopy was used to evaluate recombinant tissue-plasminogen activator (rt-PA) lysis of porcine and human clots in the same species or cross species plasma. Human and porcine whole blood clots were treated with rt-PA and an echo contrast agent, Definity®, and exposed to intermittent 120 kHz US., Results and Conclusions: The rt-PA lytic efficacy observed for porcine clots in porcine plasma was 22 times lower than for human clots in human plasma reported previously. Further, porcine clots did not exhibit increased lysis with adjuvant Definity® and US exposure. However, the rt-PA lytic susceptibility of the porcine clots in human plasma was similar to that of human clots in human plasma. Human clots perfused with porcine plasma did not respond to rt-PA, but adjuvant use of Definity® and US enhanced lysis. These results reveal considerable differences in lytic susceptibility of porcine clots and human clots to rt-PA. The use of porcine clot models to test new human thrombolytic therapies may necessitate modulation of coagulation and thrombolytic factors to reflect human hemostasis accurately.

Introduction: The objectives of this study were to compare the qualitative and quantitative profiles of herpes simplex virus type I (HSV-1) in implant surfaces between participants with peri-implantitis (PI) and Healthy peri-implant tissues and to quantitatively assess the relation between HSV-1 and periopathogens inside the microbiological profile associated with PI., Materials and Methods: A total of 40 patients with PI and 40 with healthy peri-implant tissues (HI) were recruited. Plaque samples from peri-implant sulcus and internal implant connections were analyzed using quantitative real-time polymerase chain reaction to detect and quantify HSV-1 and periodonto-pathogens. Frequencies of detection and levels of microorganisms were compared between PI and HI; the frequencies and levels of periodontopathogens were compared between HSV-1+ and HSV-1- PI to assess qualitative relations between HSV-1 and bacteria. Correlation between HSV-1 and periodontopatho-gens levels was assessed in PI and HI., Results: A total of 77 dental implants affected by PI, and 113 HIs were included. The HSV-1 prevalence was slightly higher in PI compared with controls (33.3 vs 23.8%; p > 0.05); HSV-1 was detected in external samples more frequently compared with internal samples. The HSV-1-positive patients revealed higher median loads of Prevotella intermedia (Pi) and Campylobacter rectus (Cr) compared with HSV-1-negative patients. In the PI group, a significant positive correlation was evidenced between HSV-1 and Tannerella forsythia, Parvimonas micra (Pm), Fusobacterium nucleatum, and Cr levels, while in the HI, positive correlation between HSV-1 and Aggregatibacter actinomycetemcomitans, Pi, and Pm was established., Conclusion: The HSV-1 prevalence cannot be used to identify PI. The HSV-1 was found in similar levels of PI and HI patients after an average of 6 years of loaded implants. The HSV-1 prevalence cannot be used to identify implants with or without the presence of PI., Clinical Significance: Although HSV-1 is detected in PI site, HSV-1 may represent an unspecific indicator for the host response to the bacterial challenge observed in PI.

Echogenic liposomes loaded with the thrombolytic recombinant tissue-type plasminogen activator (rt-PA) are under development for the treatment of ischemic stroke. These agents are designed to co-encapsulate cavitation nuclei to promote bubble activity in response to ultrasound exposure, and to enable localized delivery of thrombolytic. Stable cavitation improves the efficacy of the thrombolytic through enhanced fluid mixing. Echogenic liposomes that encapsulate air-filled microbubbles nucleate scant stable cavitation activity in response to 120 kHz intermittent ultrasound exposure, and have demonstrated thrombolytic efficacy equivalent to rt-PA alone. It was hypothesized that encapsulating octafluoropropane (OFP) gas within rt-PA-loaded liposomes instead of air will enhance ultrasound-mediated stable cavitation activity and increase thrombolytic efficacy compared to previous studies. The thrombolytic efficacy and cavitation activity nucleated from liposomes that encapsulate OFP microbubbles and rt-PA (OFP t-ELIP) was evaluated in vitro. Human whole blood clots were exposed to human fresh-frozen plasma alone, rt-PA (0, 0.32, 1.58, and 3.15 µg ml -1 ), or OFP t-ELIP at equivalent enzymatic activity, with and without exposure to intermittent ultrasound. Further, numerical simulations were performed to gain insight into the mechanisms of cavitation nucleation. Sustained ultraharmonic activity was nucleated from OFP t-ELIP when exposed to ultrasound. Furthermore, the thrombolytic efficacy was enhanced compared to rt-PA alone at concentrations of 1.58 µg ml -1 and 3.15 µg ml -1 (p  <  0.05). These results indicate that OFP t-ELIP can nucleate sustained stable cavitation activity and enhance the efficacy of thrombolysis.

Imaging plaque microvasculature with contrast-enhanced intravascular ultrasound (IVUS) could help clinicians evaluate atherosclerosis and guide therapeutic interventions. In this study, we evaluated the performance of chirp-coded ultraharmonic imaging using a modified IVUS system (iLab™, Boston Scientific/Scimed) equipped with clinically available peripheral and coronary imaging catheters. Flow phantoms perfused with a phospholipid-encapsulated contrast agent were visualized using ultraharmonic imaging at 12 MHz and 30 MHz transmit frequencies. Flow channels with diameters as small as 0.8 mm and 0.5 mm were visualized using the peripheral and coronary imaging catheters. Radio-frequency signals were acquired at standard IVUS rotation speed, which resulted in a frame rate of 30 frames/s. Contrast-to-tissue ratios up to 17.9 ± 1.11 dB and 10.7 ± 2.85 dB were attained by chirp-coded ultraharmonic imaging at 12 MHz and 30 MHz transmit frequencies, respectively. These results demonstrate the feasibility of performing ultraharmonic imaging at standard frame rates with clinically available IVUS catheters using chirp-coded excitation., (© The Author(s) 2015.)

Histotripsy, a form of therapeutic ultrasound that uses the mechanical action of microbubble clouds for tissue ablation, is under development to treat chronic deep vein thrombosis (DVT). We hypothesize that combining thrombolytic agents with histotripsy will enhance clot lysis. Recombinant tissue plasminogen activator (rt-PA) and rt-PA-loaded echogenic liposomes that entrain octafluoropropane microbubbles (OFP t-ELIP) were used in combination with highly shocked histotripsy pulses. Fully retracted porcine venous clots, with similar features of DVT occlusions, were exposed either to histotripsy pulses alone (peak negative pressures of 7-20 MPa), histotripsy and OFP t-ELIP, or histotripsy and rt-PA. Microbubble cloud activity was monitored with passive cavitation imaging during histotripsy exposure. The power levels of cavitation emissions from within the clot were not statistically different between treatment types, likely due to the near instantaneous rupture and destruction of OFP t-ELIP. The thrombolytic efficacy was significantly improved in the presence of rt-PA. These results suggest the combination of histotripsy and rt-PA could serve as a potent therapeutic strategy for the treatment of DVT.

Echogenic liposomes (ELIP), loaded with recombinant tissue-type plasminogen activator (rt-PA) and microbubbles that act as cavitation nuclei, are under development for ultrasound-mediated thrombolysis. Conventional manufacturing techniques produce a polydisperse rt-PA-loaded ELIP population with only a small percentage of particles containing microbubbles. Further, a polydisperse population of rt-PA-loaded ELIP has a broadband frequency response with complex bubble dynamics when exposed to pulsed ultrasound. In this work, a microfluidic flow-focusing device was used to generate monodisperse rt-PA-loaded ELIP (μtELIP) loaded with a perfluorocarbon gas. The rt-PA associated with the μtELIP was encapsulated within the lipid shell as well as intercalated within the lipid shell. The μtELIP had a mean diameter of 5 μm, a resonance frequency of 2.2 MHz, and were found to be stable for at least 30 min in 0.5 % bovine serum albumin. Additionally, 35 % of μtELIP particles were estimated to contain microbubbles, an order of magnitude higher than that reported previously for batch-produced rt-PA-loaded ELIP. These findings emphasize the advantages offered by microfluidic techniques for improving the encapsulation efficiency of both rt-PA and perflurocarbon microbubbles within echogenic liposomes.

Model-based intravascular ultrasound elastography visualizes the stress distribution within vascular tissue-information that clinicians could use to predict the propensity of atherosclerotic plaque rupture. However, there are concerns that clusters of microvessels may reduce the accuracy of the estimated stress distribution. Consequently, we have developed a contrast-enhanced intravascular ultrasound system to investigate how plaque microvasculature affects the performance of model-based elastography. In simulations, diameters of 200, 400 and 800 μm were used, where the latter diameter represented a cluster of microvessels. In phantoms, we used a microvessel with a diameter of 750 μm. Peak stress errors of 3% and 38% were incurred in the fibrous cap when stress recovery was performed with and without a priori information about microvessel geometry. The results indicate that incorporating geometric information about plaque microvasculature obtained with contrast-enhanced ultrasound imaging improves the accuracy of estimates of the stress distribution within the fibrous cap precisely., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Angioplasty and stenting of a stenosed artery enable acute restoration of blood flow. However, restenosis or a lack of re-endothelization can subsequently occur depending on the stent type. Cavitation-mediated drug delivery is a potential therapy for these conditions, but requires that particular types of cavitation be induced by ultrasound insonation. Because of the heterogeneity of tissue and stochastic nature of cavitation, feedback mechanisms are needed to determine whether the sustained bubble activity is induced. The objective of this study was to determine the feasibility of passive cavitation imaging through a metal stent in a flow phantom and an animal model. In this study, an endovascular stent was deployed in a flow phantom and in porcine femoral arteries. Fluorophore-labeled echogenic liposomes, a theragnostic ultrasound contrast agent, were injected proximal to the stent. Cavitation images were obtained by passively recording and beamforming the acoustic emissions from echogenic liposomes insonified with a low-frequency (500 kHz) transducer. In vitro experiments revealed that the signal-to-noise ratio for detecting stable cavitation activity through the stent was greater than 8 dB. The stent did not significantly reduce the signal-to-noise ratio. Trans-stent cavitation activity was also detected in vivo via passive cavitation imaging when echogenic liposomes were insonified by the 500-kHz transducer. When stable cavitation was detected, delivery of the fluorophore into the arterial wall was observed. Increased echogenicity within the stent was also observed when echogenic liposomes were administered. Thus, both B-mode ultrasound imaging and cavitation imaging are feasible in the presence of an endovascular stent in vivo. Demonstration of this capability supports future studies to monitor restenosis with contrast-enhanced ultrasound and pursue image-guided ultrasound-mediated drug delivery to inhibit restenosis., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate aetiology, demographic profile, clinical features and outcomes in cases of peripheral ulcerative keratitis (PUK)., Methods: Seventy-six eyes of 65 consecutive patients with PUK were evaluated in this prospective interventional study over an 18 month period, which were followed for 3 years. The main outcome measures were sociodemographic profile, aetiology, clinical features, management strategies and outcome., Results: Sixty per cent (39/65) of cases were men and mean age was 45.5 ± 17.9 years. Two-thirds (43/65) of the patients were from rural areas with majority (48/65) belonging to low socioeconomic status. Unilateral disease was present in 83% of patients (54/65) with nasal involvement in 60.5% (46/76) cases. The most common aetiology was Mooren's ulcer (31.5% cases (24/76 eyes)) followed by infection and systemic collagen vascular disease. Meibomian gland dysfunction (17/76: 22.3%) was the most common extraocular association and complicated cataract (12/76:15.7%) was the most common intraocular abnormality. In mild and moderate cases, no significant visual improvement was observed (p = 0.085 and p = 0.156) as compared with the pretreatment status. Surgical treatment was successful in maintaining anatomical integrity in 83.3% (30/36) eyes. Recurrence of the disease was seen in one eye in moderate disease and three eyes in severe disease., Conclusions: Mooren's ulcer followed by collagen vascular diseases and infection are important causes of PUK in developing countries. Surgical intervention in perforated cases had good anatomical success and visual prognosis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

The purpose of this study was to describe a modified technique of sutureless DSAEK with continuous pressurized internal air tamponade. This was a prospective interventional case series, single-center, institutional study. Twenty-seven patients with corneal decompensation without scarring were included. Aphakic patients and patients with cataractous lens requiring IOL implantation surgery were excluded. Following preparation of the donor tissue, a corneal tunnel was made nasally with two side ports. All incisions were kept long enough to be overlapped by the peripheral part of the donor tissue. Descemet membrane scoring was done using a reverse Sinskey hook, following which it was removed with the same instrument or by forceps. The donor lenticule was then inserted using Busin's glide. Continuous pressurized internal air tamponade was achieved by means of a 30-gauge needle, inserted through the posterior limbus, for 12-14 min. At the end of the surgery, air was partially replaced with BSS, leaving a moderate-sized mobile air bubble in the anterior chamber. At the 6 month's follow-up, CDVA improved from counting fingers at half meter-6/24 preoperatively to 6/9-6/18 postoperatively, and the mean endothelial cell count decreased: to 1,800 from 2,200 cell/mm(2) preoperatively (18.19 % endothelial cell loss). Donor lenticule thickness as documented on AS-OCT was 70-110 µ on Day 1 and 50-80 µ at 6 months postoperative. None of the cases had flat AC or peripheral anterior synechiae formation. None of the patients required a second intervention. There were no cases of primary graft failure, pupillary block glaucomax or donor lenticule dislocation postoperatively. Our modified technique is simple and effective with reduction in postoperative complications associated with DSAEK, thereby maximizing anatomic and functional outcomes associated.

Type 2 diabetes mellitus patients (T2D) have elevated risk of stroke, suggesting that cerebrovascular function is impaired. Herein, we examined dynamic cerebral autoregulation (CA) at rest and during exercise in T2D patients and determined whether underlying systemic oxidative stress is associated with impairments in CA. Middle cerebral artery blood velocity and arterial blood pressure (BP) were measured at rest and during 2-min bouts of low- and high-intensity isometric handgrip performed at 20% and 40% maximum voluntary contraction, respectively, in seven normotensive and eight hypertensive T2D patients and eight healthy controls. Dynamic CA was estimated using the rate of regulation (RoR). Total reactive oxygen species (ROS) and superoxide levels were measured at rest. There were no differences in RoR at rest or during exercise between normotensive and hypertensive T2D patients. However, when compared with controls, T2D patients exhibited lower RoR at rest and during low-intensity handgrip indicating impaired dynamic CA. Moreover, the RoR was further reduced by 29 ± 4% during high-intensity handgrip in T2D patients (0.307 ± 0.012/s rest vs. 0.220 ± 0.014/s high intensity; P < 0.01), although well maintained in controls. T2D patients demonstrated greater baseline total ROS and superoxide compared with controls, both of which were negatively related to RoR during handgrip (e.g., total ROS: r = -0.71, P < 0.05; 40% maximum voluntary contraction). Collectively, these data demonstrate impaired dynamic CA at rest and during isometric handgrip in T2D patients, which may be, in part, related to greater underlying systemic oxidative stress. Additionally, dynamic CA is blunted further with high intensity isometric contractions potentially placing T2D patients at greater risk for cerebral events during such activities., (Copyright © 2015 the American Physiological Society.)

Several studies have demonstrated that blacks exhibit elevations in systemic oxidative stress. However, the source(s) and mechanism(s) contributing to the elevation in oxidative stress remain unclear. Given that peripheral blood mononuclear cells (PBMCs) can be a major source of NADPH oxidase-derived superoxide production, we tested the hypothesis that young black men demonstrate greater superoxide production and NADPH oxidase expression in PBMCs compared with whites. PBMCs were freshly isolated from whole blood in young normotensive black (n = 18) and white (n = 16) men. Intracellular superoxide production in PBMCs was measured using dihydroethidium fluorescence, protein expression of NADPH oxidase subunits, gp91(phox) (membranous) and p47(phox) (cytosolic) in PBMCs were assessed using Western blot analysis, and plasma protein carbonyls were measured as a marker of systemic oxidative stress. Black men showed elevated intracellular superoxide production (4.3 ± 0.5 vs. 2.0 ± 0.6 relative fluorescence units; black men vs. white men, P < 0.05), increased protein expression for gp91(phox) and p47(phox) (e.g., p47(phox): 1.1 ± 0.2, black men vs. 0.4 ± 0.1, white men, P < 0.05) in PBMCs and higher circulating protein carbonyl levels (22 ± 4 vs. 14 ± 2 nmol/ml; black men vs. white men, P < 0.05). Interestingly, a positive family history of hypertension in black men did not further enhance PBMC-derived intracellular superoxide production or NADPH oxidase subunit protein expression. These findings indicate that black men exhibit greater resting PBMC-derived superoxide production and an upregulation of the NADPH oxidase pathway with a possible contribution to increases in systemic oxidative stress., (Copyright © 2015 the American Physiological Society.)

Characterizing the non-linear response of microbubble contrast agents is important for their efficacious use in imaging and therapy. In this article, we report that the subharmonic and ultraharmonic response of lipid-shelled microbubble contrast agents exhibits a strong temporal dependence. We characterized non-linear emissions from Targestar-p microbubbles (Targeson Inc., San Diego, CA, USA) periodically for 60 min, at 10 MHz excitation frequency. The results revealed a considerable increase in the subharmonic and ultraharmonic response (nearly 12-15 and 5-8 dB) after 5-10 min of agent preparation. However, the fundamental and the harmonic response remained almost unchanged in this period. During the next 50 min, the subharmonic, fundamental, ultraharmonic, and harmonic responses decreased steadily by 2-5 dB. The temporal changes in the non-linear behavior of the agent appeared to be primarily mediated by gas-exchange through the microbubble shell; temperature and prior acoustic excitation based mechanisms were ruled out. Further, there was no measurable change in the agent size distribution by static diffusion. We envisage that these findings will help obtain reproducible measurements from agent characterization, non-linear imaging, and fluid-pressure sensing. These findings also suggest the possibility for improving non-linear imaging by careful design of ultrasound contrast agents., (Published by Elsevier Inc.)

Objective: To review the risk factors, management, and visual outcomes of pediatric chemical eye injuries in a tertiary care hospital in North India., Design: Retrospective hospital-based study., Participants: Patients aged <16 years with ocular chemical burns., Methods: Case records of patients with ocular chemical injury who presented to the Dr. Rajendra Prasad Centre for Ophthalmic Sciences were reviewed over a 5-year period., Main Outcome Measures: Demographic profile, nature of chemical injury, complications, and visual outcomes after chemical injury., Results: A total of 134 pediatric patients with a history of ocular chemical burns were seen between March 2006 and March 2011. The mean age of patients at the time of injury was 8.95±4.89 years (range, 1.2-15.5 years); 63.4% were male. Sixty-nine patients (51.4%) belonged to the preschool (0-5 years) age group. Bilateral chemical injuries were seen in 24 patients (17.9%). Lime ("chuna") was the most commonly involved chemical (88, 65.6%) followed by toilet cleaner (20, 14.9%). The mean time between injury and presentation was 68.3 days (range, 1-365 days). Severe (grade 3 and 4) ocular chemical injury was seen in 94 patients (70.1%). Surgical intervention was performed in 114 eyes (85%) in the form of amniotic membrane grafting (n = 78), symblepharon release (n = 56), limbal stem cell transplantation (n = 26), and lamellar keratoplasty (n = 14). The average number of surgeries conducted per patient was 2.3 (range, 1-4). Median visual acuity at final follow-up (mean, 537±354 days) was 3/60., Conclusions: Chemical injuries in pediatric patients are more commonly encountered in the preschool age group and are associated with severe visual loss. Alkali injury from bursting of chuna packets was the most common mode of injury in pediatric patients in our study., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Many diseases associated with sympathoexcitation also exhibit elevated reactive oxygen species (ROS). A recent animal study indicated that exogenous administration of the sympathetic neurotransmitter norepinephrine (NE) increased systemic ROS via circulating leukocytes. The mechanisms contributing to this effect of NE and whether these findings can be translated to humans is unknown. Thus we tested the hypothesis that NE increases superoxide production in human peripheral blood mononuclear cells (PBMCs) via NADPH oxidase. Primary human PBMCs were freshly isolated from healthy young men and placed in culture. After NE (50 pg/ml, 50 ng/ml, and 50 μg/ml concentrations) or control treatments, NADPH oxidase mRNA expression (gp91(phox), p22(phox), and p67(phox)) was assessed using real-time RT-PCR, and intracellular superoxide production was measured using dihydroethidium fluorescence. PBMCs were also treated with selective adrenergic agonists-antagonists to determine the receptor population involved. In addition, CD14(+) monocyte-endothelial cell adhesion was determined using a fluorescent-based assay. NE significantly increased NADPH oxidase gene expression and intracellular superoxide production in a time-dependent manner (superoxide: 0.9 ± 0.2 fold, 6 h vs. 3.0 ± 0.3 fold, 36 h; NE, 50 μg/ml; P < 0.05). The sustained increase in NE-induced superoxide production was primarily mediated via α-adrenergic receptors, preferentially α2-receptors. The NADPH oxidase blocker diphenylene iodonium and protein kinase C inhibitor Staurosporine significantly attenuated NE-induced increases in superoxide production. Importantly, NE treatment increased CD14(+) monocyte-endothelial cell adhesion. These findings indicate for the first time that NE increases superoxide production in freshly isolated primary human PBMCs via NADPH oxidase through α-adrenergic receptors, an effect facilitating monocyte adhesion to the endothelium.

Purpose: Subharmonic imaging is of interest for high frequency (>10 MHz) nonlinear imaging, because it can specifically detect the response of ultrasound contrast agents (UCA). However, conventional UCA produce a weak subharmonic response at high frequencies, which limits the sensitivity of subharmonic imaging. We hypothesized that modifying the size distribution of the agent can enhance its high-frequency subharmonic response. The overall goal of this study was to investigate size-manipulated populations of the agent to determine the range of sizes that produce the strongest subharmonic response at high frequencies (in this case, 20 MHz). A secondary goal was to assess whether the number or the volume-weighted size distribution better represents the efficacy of the agent for high-frequency subharmonic imaging., Methods: The authors created six distinct agent size distributions from the native distribution of a commercially available UCA (Targestar-P®). The median (number-weighted) diameter of the native agent was 1.63 μm, while the median diameters of the size-manipulated populations ranged from 1.35 to 2.99 μm. The authors conducted acoustic measurements with native and size-manipulated agent populations to assess their subharmonic response to 20 MHz excitation (pulse duration 1.5 μs, pressure amplitudes 100-398 kPa)., Results: The results showed a considerable difference between the subharmonic response of the agent populations that were investigated. The subharmonic response peaked for the agent population with a median diameter of 2.15 μm, which demonstrated a subharmonic signal that was 8 dB higher than the native agent. Comparing the subharmonic response of different UCA populations indicated that microbubbles with diameters between 1.3 and 3 μm are the dominant contributors to the subharmonic response at 20 MHz. Additionally, a better correlation was observed between the subharmonic response of the agent and the number-weighted size-distribution (R2=0.98) than with the volume-weighted size distribution (R2=0.53)., Conclusions: Modifying the size distribution of the agent appears to be a viable strategy to improve the sensitivity of high-frequency subharmonic imaging. In addition, when the size distribution of the UCA has not been suitably modified, the number-weighted size distribution is a useful parameter to accurately describe the efficacy of the agent for high-frequency subharmonic imaging.

Purpose: To report the feasibility and outcome of lens aspiration, and Fugo blade-assisted capsulotomy and anterior vitrectomy in eyes with anterior persistent hyperplastic primary vitreous (PHPV)., Materials and Methods: In this case series, 10 eyes of 10 patients with anterior PHPV underwent lens aspiration. The vascularized posterior capsule was cut with a Fugo blade (plasma knife) and removed with a vitrector. A foldable posterior chamber intraocular lens (IOL) was implanted in eight eyes and the outcomes were evaluated., Results: The mean age of patients was 16.8 ± 6.37 months (range: 5 to 28 months). The surgery was completed successfully in all eyes. There were no cases of intraocular hemorrhage intraoperatively. Foldable acrylic IOL was implanted in the bag in 3 eyes and in the sulcus in 5 eyes. Two eyes were microphthalmic and did no undergo IOL implantation (aphakic). None of the eyes had a significant reaction or elevated intraocular pressure postoperatively. The follow-up ranged from 4 to 21 months. All the pseudophakic eyes achieved a best corrected visual acuity of ≥20/200 with 50% (4/8) of these eyes with ≥20/60 vision., Conclusion: Lens aspiration followed by posterior capsulotomy with Fugo blade-assisted plasma ablation is a feasible technique for performing successful lens surgery in cases with florid anterior PHPV.

The current excitation strategy for harmonic and subharmonic imaging (HI and SHI) uses short sine-bursts. However, alternate pulsing strategies may be useful for enhancing nonlinear emissions from ultrasound contrast agents. The goal of this study was to corroborate the hypothesis that chirp-coded excitation can improve the performance of high-frequency HI and SHI. A secondary goal was to understand the mechanisms that govern the response of ultrasound contrast agents to chirp-coded and sine-burst excitation schemes. Numerical simulations and acoustic measurements were conducted to evaluate the response of a commercial contrast agent (Targestar-P(®)) to chirp-coded and sine-burst excitation (10 MHz frequency, peak pressures 290 kPa). The results of the acoustic measurements revealed an improvement in signal-to-noise ratio by 4 to 14 dB, and a two- to threefold reduction in the subharmonic threshold with chirp-coded excitation. Simulations conducted with the Marmottant model suggest that an increase in expansion-dominated radial excursion of microbubbles was the mechanism responsible for the stronger nonlinear response. Additionally, chirp-coded excitation detected the nonlinear response for a wider range of agent concentrations than sine-bursts. Therefore, chirp-coded excitation could be a viable approach for enhancing the performance of HI and SHI.

An unusual presentation of a life-threatening cerebellopontine abscess shows the importance of re-evaluating existing diagnoses when the clinical picture changes. Despite being rare, brain abscess is a potentially fatal condition that requires early radiological and surgical intervention. It has a varied presentation, with many cases showing no localising typical features, making it hard to diagnose at presentation. A high index of suspicion should be applied to cases exhibiting rapidly changing neurology. This is the first reported case of cerebellopontine abscess with no primary infective foci.

Despite standard drug therapy, sympathetic nerve activity (SNA) remains high in heart failure (HF) patients making the sympathetic nervous system a primary drug target in the treatment of HF. Studies in rabbits with pacing-induced HF have demonstrated that statins reduce resting SNA, in part, due to reductions in reactive oxygen species (ROS). Whether these findings can be extended to the clinical setting of human HF remains unclear. We first performed a study in seven statin-naïve HF patients (56 ± 2 yr; ejection fraction: 31 ± 4%) to determine if 1 mo of simvastatin (40 mg/day) reduces muscle SNA (MSNA). Next, to control for possible placebo effects and determine the effect of simvastatin on ROS, a double-blinded, placebo-controlled crossover design study was performed in six additional HF patients (51 ± 3 yr; ejection fraction: 22 ± 4%), and MSNA, ROS, and superoxide were measured. We tested the hypothesis that statin therapy decreases resting MSNA in HF patients and this would be associated with reductions in ROS. In study 1, simvastatin reduced resting MSNA (75 ± 5 baseline vs. 65 ± 5 statin bursts/100 heartbeats; P < 0.05). Likewise, in study 2, simvastatin also decreased resting MSNA (59 ± 5 placebo vs. 45 ± 6 statin bursts/100 heartbeats; P < 0.05). In addition, statin therapy significantly reduced total ROS and superoxide. As expected, cholesterol was reduced after simvastatin. Collectively, these findings indicate that short-term statin therapy concomitantly reduces resting MSNA and total ROS and superoxide in HF patients. Thus, in addition to lowering cholesterol, statins may also be beneficial in reducing sympathetic overactivity and oxidative stress in HF patients.

Purpose: To evaluate the outcomes of intrascleral haptic fixation of an intraocular lens (IOL) with fibrin glue combined with penetrating keratoplasty (PKP) or Descemet-stripping automated endothelial keratoplasty (DSAEK) for aphakic or pseudophakic bullous keratopathy (BKP)., Setting: Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India., Design: Case series., Methods: Eyes with BKP had combined PKP or DSAEK with fibrin glue-assisted intrascleral posterior chamber (PC) IOL fixation; PKP was performed in eyes with a corneal scar and DSAEK in eyes without a scar. The parameters evaluated were corrected distance visual acuity (CDVA), anterior segment biomicroscopy, intraocular pressure, central corneal thickness (CCT), and IOL status. Intraoperative events and postoperative complications were recorded., Results: The study evaluated 11 patients (11 eyes). Intrascleral fixation of a PC IOL with PKP or DSAEK was successfully performed in all eyes; PKP was performed in 6 eyes (54.54%) and DSAEK in 5 eyes. The mean CDVA improved from 1.95 logMAR ± 0.29 (SD) to 0.40 ± 0.16 logMAR (P<.001). The mean CCT was 0.741 ± 0.71 mm preoperatively and 0.579 ± 0.20 mm postoperatively (P<.001). There were no cases of intraoperative or postoperative IOL decentration or other complications., Conclusions: Fibrin glue-assisted intrascleral fixation of a PC IOL combined with DSAEK or PKP was a safe, effective method to manage BKP with aphakia or malpositioned IOLs. The IOL fixation was strong enough to sustain the manipulation required for corneal procedures., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: Subharmonic intravascular ultrasound imaging (S-IVUS) could visualize the adventitial vasa vasorum, but the high pressure threshold required to incite subharmonic behavior in an ultrasound contrast agent will compromise sensitivity-a trait that has hampered the clinical use of S-IVUS. The purpose of this study was to assess the feasibility of using coded-chirp excitations to improve the sensitivity and axial resolution of S-IVUS., Methods: The subharmonic response of Targestar-p(TM), a commercial microbubble ultrasound contrast agent (UCA), to coded-chirp (5%-20% fractional bandwidth) pulses and narrowband sine-burst (4% fractional bandwidth) pulses was assessed, first using computer simulations and then experimentally. Rectangular windowed excitation pulses with pulse durations ranging from 0.25 to 3 μs were used in all studies. All experimental studies were performed with a pair of transducers (20 MHz/10 MHz), both with diameter of 6.35 mm and focal length of 50 mm. The size distribution of the UCA was measured with a Casy(TM) Cell counter., Results: The simulation predicted a pressure threshold that was an order of magnitude higher than that determined experimentally. However, all other predictions were consistent with the experimental observations. It was predicted that: (1) exciting the agent with chirps would produce stronger subharmonic response relative to those produced by sine-bursts; (2) increasing the fractional bandwidth of coded-chirp excitation would increase the sensitivity of subharmonic imaging; and (3) coded-chirp would increase axial resolution. The experimental results revealed that subharmonic-to-fundamental ratios obtained with chirps were 5.7 dB higher than those produced with sine-bursts of similar duration. The axial resolution achieved with 20% fractional bandwidth chirps was approximately twice that achieved with 4% fractional bandwidth sine-bursts., Conclusions: The coded-chirp method is a suitable excitation strategy for subharmonic IVUS imaging. At the 20 MHz transmission frequency and 20% fractional bandwidth, coded-chirp excitation appears to represent the ideal tradeoff between subharmonic strength and axial resolution.

It is presently unknown whether there are sex differences in the magnitude of blood pressure (BP) responses to baroreceptor perturbation or if the relative contribution of cardiac output (CO) and total vascular conductance (TVC) to baroreflex-mediated changes in BP differs in young women and men. Since sympathetic vasoconstrictor tone is attenuated in women, we hypothesized that carotid baroreflex-mediated BP responses would be attenuated in women by virtue of a blunted vascular response (i.e., an attenuated TVC response). BP, heart rate (HR), and stroke volume were continuously recorded during the application of 5-s pulses of neck pressure (NP; carotid hypotension) and neck suction (NS; carotid hypertension) ranging from +40 to -80 Torr in women (n = 20, 21 ± 0.5 yr) and men (n = 20, 21 ± 0.4 yr). CO and TVC were calculated on a beat-to-beat basis. Women demonstrated greater depressor responses to NS (e.g., -60 Torr, -17 ± 1%baseline in women vs. -11 ± 1%baseline in men, P < 0.05), which were driven by augmented decreases in HR that, in turn, contributed to larger reductions in CO (-60 Torr, -15 ± 2%baseline in women vs. -6 ± 2%baseline in men, P < 0.05). In contrast, pressor responses to NP were similar in women and men (e.g., +40 Torr, +14 ± 2%baseline in women vs. +10 ± 1%baseline in men, P > 0.05), with TVC being the primary mediating factor in both groups. Our findings indicate that sex differences in the baroreflex control of BP are evident during carotid hypertension but not carotid hypotension. Furthermore, in contrast to our hypothesis, young women exhibited greater BP responses to carotid hypertension by virtue of a greater cardiac responsiveness.

Nutrient intake is accompanied by increases in central sympathetic outflow, a response that has been mainly attributed to insulin. Insulin-mediated sympathoexcitation appears to be blunted in insulin-resistant conditions, suggesting that aside from peripheral insulin insensitivity, such conditions may also impair the central action of insulin in mediating sympathetic activation. What remains unclear is whether an insulin-sensitive state, such as that induced by chronic endurance training, alters the central sympathetic effects of insulin during postprandial conditions. To examine this question plasma insulin and glucose, muscle sympathetic nerve activity (MSNA), heart rate, and arterial blood pressure were measured in 11 high-fit [HF; peak oxygen uptake (V(O(2peak))) 65.9 +/- 1.4 ml x kg(-1) x min(-1)] and 9 average-fit (AF; V(O(2peak)) 43.6 +/- 1.3 ml x kg(-1) x min(-1)) male subjects before and for 120 min after ingestion of a mixed meal drink. As expected, the insulin response to meal ingestion was lower in HF than AF participants (insulin area under the curve(0-120): 2,314 +/- 171 vs. 4,028 +/- 460 microIU x ml(-1) x 120(-1), HF vs. AF, P < 0.05), with similar plasma glucose responses between groups. Importantly, following consumption of the meal, the HF subjects demonstrated a greater rise in MSNA compared with the AF subjects (e.g., 120 min: Delta21 +/- 1 vs. 8 +/- 3 bursts/100 heart beats, HF vs. AF, P < 0.05). Furthermore, when expressed relative to plasma insulin, HF subjects exhibited a greater change in MSNA for any given change in insulin. Arterial blood pressure responses following meal intake were similar between groups. Collectively, these data suggest that, in addition to improved peripheral insulin sensitivity, endurance training may enhance the central sympathetic effect of insulin to increase MSNA following consumption of a mixed meal.

Cerebellar haemangioblastomas are rare in the elderly. Those associated with the von Hippel-Lindau (VHL) disease, usually present during the third decade of life. We report an unusually delayed presentation in an 80 year old obligate carrier of VHL gene mutation.